ST-segment elevation acute myocardial infarction: clinical guidelines

Applies toadults2024 editionI21.0, I21.1, I21.2, I21.3…

Clinical guidelines of the Russian Ministry of Health, adults. 2024 edition, ICD-10 codes: I21.0, I21.1, I21.2, I21.3…. The page features an abridged version by WhiteCoat Pro and the full official text.

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Brief for Practice

WhiteCoat Pro editorial summary based on the 2024 guideline text. Each item links to the original section — verify against it before prescribing.

STEMI is typically the result of persistent thrombotic occlusion of a major coronary artery, carrying the risk of fatal arrhythmias, acute heart failure, and myocardial rupture. Management centers on rapidly recognizing STEMI based on clinical presentation and ECG, proceeding with reperfusion without waiting for troponin, and restoring blood flow as early as possible via primary PCI or a pharmacoinvasive strategy.

Key points

STEMI: symptoms of myocardial ischemia plus persistent ST elevation >20 min in at least 2 contiguous leads or newly onset LBBB; STEMI also includes newly onset LBBB. → in the text
An ECG must be recorded and interpreted within 10 minutes of first medical contact; a minimum of 12 standard leads is required, with V7–V9 and V3R–V4R added if posterior or right ventricular MI is suspected. ESC IB/IA, LOR C/A. → in the text
Troponin T/I is required to confirm the nosological diagnosis of MI, but the decision to perform thrombolysis or primary PCI should not be delayed for the results. ESC 1B, LOR A, LoE 1. → in the text
Reperfusion is indicated for all patients with STEMI and symptom onset within 12 hours. Primary PCI is preferred if the time from diagnosis to the guidewire crossing the infarct-related artery is ≤120 minutes. ESC IA. → in the text
If primary PCI cannot be performed within 120 minutes and symptoms are of ≤12 hours' duration, IV thrombolysis should be initiated as rapidly as possible — within 10 minutes of diagnosis — in the absence of contraindications. ESC IA, LOR A, LoE 1. → in the text
Following successful thrombolysis, coronary angiography with the intent to perform PCI is required within 2–24 hours; if thrombolysis fails at 60–90 minutes (ST-segment resolution <50% or absent), urgent coronary angiography and "rescue" PCI are indicated, and thrombolysis should not be repeated. ESC IA. → in the text
Primary PCI must include intervention on the infarct-related artery; radial access and stenting are preferred, ideally using a next-generation drug-eluting stent. ESC IA, LOR A. → in the text

Diagnostics

First, assess pain or equivalents of ischemia: retrosternal pain or pressure radiating to the neck, lower jaw, or left arm; dyspnea, epigastric pain, nausea, and weakness may occur. Relief of pain with nitroglycerin does not rule out STEMI. ESC IC, LOR C. → in the text
Record the time from the start of the last pain episode to medical contact — this dictates the choice of reperfusion strategy. → in the text
Perform an ECG at the site of first contact within 10 minutes and interpret it; if difficulties arise, transmit the ECG for telemedical interpretation. ESC IB, LOR C. → in the text
Criteria for ST elevation: J-point elevation ≥0.1 mV in at least 2 contiguous leads, excluding V2–V3; thresholds for V2–V3: men ≥40 years ≥0.2 mV, men <40 years ≥0.25 mV, women ≥0.15 mV. → in the text
If the standard ECG is uninformative but suspicion remains, use leads V7–V9 and V3R–V4R; in the event of ongoing or recurrent symptoms, repeat the ECG (e.g., every 15–30 minutes during the first hour) or perform continuous ST-segment monitoring. → in the text
Determine troponin T/I using a quantitative assay; the diagnosis of acute MI is confirmed by a rise and/or fall in troponin values exceeding the 99th percentile upper reference limit, or an increase >20% if baseline levels are stably elevated, in conjunction with ischemic criteria. ESC 1B, LOR A. → in the text
In the hospital, perform echocardiography to assess left ventricular ejection fraction, optimally within the first 24 hours; if myocardial rupture or ascending aortic dissection is suspected, perform it emergently prior to coronary angiography. ESC 1C, LOR C. → in the text

Treatment

Within the first 12 hours, perform primary PCI if feasible: target diagnosis-to-guidewire time ≤120 minutes; ≤60 minutes in a PCI center, and ≤90 minutes when transferred from a non-percutaneous hospital. ESC IA. → in the text
If PCI cannot be performed within 120 minutes and symptoms are present for ≤12 hours, initiate IV thrombolysis within 10 minutes of diagnosis; fibrin-specific thrombolytics are preferred over non-fibrin-specific ones. In patients older than 75 years, tenecteplase is administered at half the standard dose. ESC IA/IB/IIaB. → in the text
Aspirin is administered to all patients without contraindications: a loading dose of 150–300 mg chewed and swallowed as soon as possible, followed by 75–100 mg orally once daily indefinitely starting on day two. ESC IA, LOR A, LoE 1. → in the text
In patients undergoing thrombolysis, clopidogrel is added to aspirin before or during thrombolysis: a loading dose of 300 mg orally, followed by 75 mg once daily for 12 months; in patients >75 years, no loading dose is given. ESC IB, LOR A. → in the text
With invasive reperfusion or no reperfusion, a P2Y12 inhibitor is added to aspirin for 12 months, provided there is no high bleeding risk: prasugrel 60 mg loading dose and 10 mg/day orally in patients undergoing coronary stenting; ticagrelor 180 mg loading dose and 90 mg twice daily orally for invasive reperfusion or absent reperfusion; clopidogrel 600 mg for PCI or 300 mg without PCI, followed by 75 mg/day if ticagrelor or prasugrel are contraindicated, not tolerated, or unavailable. ESC IA/IB. → in the text
Anticoagulant therapy should be started parenterally once STEMI is confirmed. For PCI, unfractionated heparin is administered at 70–100 IU/kg IV bolus; enoxaparin may be an alternative, whereas fondaparinux should not be used for primary PCI. ESC IA/IC/IIaB/IIIB. → in the text
Severe pain is managed with IV morphine: dilute 10 mg in at least 10 ml of 0.9% NaCl; administer an initial 2–4 mg slowly, followed by repeated doses of 2–4 mg every 5–15 minutes as needed until relief is achieved or adverse reactions occur. ESC IIaB, LOR C. → in the text
Initiate high-intensity statin therapy within the first 24 hours of hospitalization regardless of baseline cholesterol levels: atorvastatin 40–80 mg/day or rosuvastatin 20–40 mg/day; target LDL-C after STEMI is <1.4 mmol/L with a reduction of at least 50%. ESC IA, LOR A. → in the text

When to refer and how to monitor

Any suspicion of STEMI is an indication for emergency hospitalization; patient routing must ensure direct admission or rapid transfer to a hospital capable of invasive ACS management. → in the text
If a patient with suspected STEMI is admitted to a hospital without emergency revascularization capabilities, they must be transferred in a timely manner to an institution where ACS revascularization is performed. ESC IC, LOR C. → in the text
Following thrombolysis, even if successful, the patient must be immediately hospitalized or transferred to a facility with 24/7 PCI capabilities. ESC IA, LOR A. → in the text
Early discharge after primary PCI is feasible in selected low-risk patients without early complications, provided organized rehabilitation and follow-up are in place; a Zwolle score ≤3 indicates a 30-day mortality risk of 0.5%, allowing discharge within the first 72 hours. ESC IB, LOR A. → in the text
Following discharge, all STEMI patients require follow-up care; for the first 12 months, this should be with a cardiologist at least twice a year, followed by lifelong follow-up with a general practitioner/family physician with cardiologist consultations as indicated. ESC IC, LOR C. → in the text

Frequently asked questions

Should troponin be awaited before performing reperfusion in STEMI?

No. Troponin is required for the formal confirmation of an MI diagnosis, but thrombolysis or primary PCI should not be delayed for the results if the clinical presentation and ECG are consistent with STEMI. → in the text

When should thrombolysis be chosen instead of primary PCI?

When no more than 12 hours have elapsed since symptom onset, and primary PCI with a guidewire crossing the infarct-related artery cannot be performed within 120 minutes of diagnosis. Thrombolysis is initiated within 10 minutes of diagnosis in the absence of contraindications. → in the text

How to determine if thrombolysis was successful?

A practical criterion is a reduction in ST-segment elevation by 50% or more in the lead with the maximum initial elevation within 90 minutes of starting thrombolysis. If no reduction or a <50% reduction is observed at 60–90 minutes, urgent coronary angiography with "rescue" PCI is indicated. → in the text

Who should receive oxygen in STEMI?

Oxygen is indicated in the presence of hypoxemia: SpO2 <90% or PaO2 <60 mmHg; humidified oxygen is administered at 2–8 L/min via nasal cannula. Routine oxygen therapy is not indicated when SpO2 ≥90%. → in the text

What secondary prevention measures are mandatory after STEMI?

Key elements in guidelines include: long-term aspirin, dual antiplatelet therapy typically for 12 months in the absence of contraindications, high-intensity statin therapy targeting LDL-C <1.4 mmol/L with a ≥50% reduction, ACE inhibitors/ARBs as indicated, beta-blockers at least for LVEF ≤40%, cardiac rehabilitation, and risk factor control. → in the text

Status: Applied · approved by the Scientific and Practical Council of the Russian Ministry of Health
Database ID: 157, revision 5 (ID 157_5)
Publication date: November 25, 2024
Age category: adults
ICD-10 codes: I21.0 I21.1 I21.2 I21.3 I21.9 I22.0 I22.1 I22.8 I22.9 I24.0 I24.8 I24.9
Specialties: Cardiology Cardiovascular Surgery Emergency Medicine
Developers: Association of Cardiovascular Surgeons of Russia
All-Russian Public Organization «Russian Society of Cardiology»
Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists
All-Russian Public Organization «Russian Society of Emergency Medicine»
Official text: Russian Ministry of Health Guidelines Rubricator — 157_5

Abbreviated Clinical Guidelines: ST-Segment Elevation Myocardial Infarction

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1.1. Definition of the disease or condition

Acute Coronary Syndrome (ACS)

Definition: A term denoting any group of clinical signs or symptoms suggesting myocardial infarction (MI) or unstable angina (UA).
Application:
Used as a provisional diagnosis during the first hours and days of the disease, when data are insufficient for a nosological diagnosis («MI» or «UA»).
Subsequently transforms into a definitive diagnosis: «acute MI», «UA», or another diagnosis (including non-cardiological) based on differential diagnosis results.
Clinical Presentation Patterns:
Destabilization of chronic coronary artery disease (CAD).
First manifestation of coronary artery disease (in patients without prior symptoms).

ACS with Persistent ST-Segment Elevation (STEMI)

Definition: Acute clinical signs of myocardial ischemia combined with specific ECG changes.
ECG Criteria:
Persistent (duration > 20 minutes) ST-segment elevation in at least two contiguous leads.
OR newly onset left bundle branch block (LBBB).

Myocardial Infarction (MI)

Definition: Acute myocardial injury due to ischemia.
Diagnostic Criteria for Acute MI (not related to percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]):
Documentation of a rise and/or fall in blood cardiac troponin concentration is required.
Threshold Values:
In patients with no baseline elevation: At least one value exceeding the 99th percentile of the upper reference limit.
In patients with a chronically elevated baseline level (variability le 20%): Concentration increase and/or decrease > 20%.
Mandatory Condition: Troponin dynamics must be accompanied by at least one criterion of acute myocardial ischemia.

Criteria for Myocardial Infarction

The diagnosis is confirmed if one of the following features is present:

Newly onset (or presumed new) ischemic ECG changes.
Development of pathological Q waves on the ECG.
Imaging: evidence of new areas of myocardial viability loss or regional wall motion abnormalities of ischemic etiology.
Thrombosis: detection of an intracoronary thrombus on coronary angiography (CAG) or autopsy.

> Note: For detailed MI criteria, see Appendix A3 [5].

ECG Criteria for Myocardial Infarction

Changes must be recorded in at least two contiguous leads.

1. ST-Segment Elevation

Newly onset elevation measured at the J point.

All leads (except V2–V3): ge 0.1 mV (1 mm).
Leads V2–V3:
Men ge 40 years: ge 0.2 mV (2 mm).
Men < 40 years: ge 0.25 mV (2.5 mm).
Women (any age): ge 0.15 mV (1.5 mm).

> Condition: In the absence of left ventricular hypertrophy (LVH) or left bundle branch block (LBBB).

2. ST Depression and T-Wave Changes

ST Depression: Newly onset horizontal or downsloping depression ge 0.05 mV (0.5 mm).
T-Wave Inversion: ge 0.1 mV (1 mm) in leads with a dominant R wave (or R/S ratio > 1).

ST-Elevation Myocardial Infarction (STEMI)

Definition: MI characterized in the early stages by persistent (> 20 minutes) ST-segment elevation ge in two contiguous leads.

Patients with newly onset LBBB are also included in this category.

Pathophysiology:

Caused by acute complete occlusion of a major coronary artery branch.
Causes transmural ischemic injury.
Without revascularization (PCI, CABG, thrombolysis), transmural necrosis develops.

Risks:

High risk of death from:

Fatal rhythm and conduction disorders.
Myocardial rupture.
Acute heart failure (AHF).

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List of Abbreviations

AS – atherosclerotic plaque

AV – atrioventricular

ACT – activated clotting time

AH – arterial hypertension

BP – blood pressure

ADP – adenosine diphosphate

ACE – angiotensin-converting enzyme

ASA – acetylsalicylic acid**

aPTT – activated partial thromboplastin time

ARB – angiotensin II receptor blocker

CVD – cardiovascular disease

IABP – intra-aortic balloon counterpulsation

IV – intravenous

HIV – human immunodeficiency virus

IVUS – intravascular ultrasound (syn.: intravascular coronary ultrasound)

HMG-CoA reductase – 3-hydroxy-3-methylglutaryl-coenzyme A reductase

GP IIb/IIIa – glycoproteins IIb/IIIa

PCWP – pulmonary capillary wedge pressure

IU (units) – international units

ЕОК – European Society of Cardiology

VT – ventricular tachycardia

ACE inhibitor – angiotensin-converting enzyme inhibitor

CHD – coronary heart disease

IMV – mechanical ventilation

ИМ – myocardial infarction

NSTEMI – myocardial infarction without persistent ST-segment elevation on ECG

MINOCA – myocardial infarction with non-obstructive coronary arteries

STEMI – myocardial infarction with persistent ST-segment elevation on ECG

CA – coronary artery

CAG – coronary angiography

ICD – implantable cardioverter-defibrillator (single-chamber implantable cardioverter-defibrillator***; dual-chamber implantable cardioverter-defibrillator***; triple-chamber (biventricular) implantable cardioverter-defibrillator***)

CrCl – creatinine clearance (assessment of nephron function via creatinine clearance (Rehberg's test) or estimated within a blood creatinine test)

CR – cardiac rehabilitation

CT – computed tomography (computed tomography of the chest organs; computed tomography of the chest organs with intravenous bolus contrast enhancement; computed tomography of the chest with intravenous bolus contrast enhancement, multiplanar and three-dimensional reconstruction)

CCTA – coronary computed tomography angiography

CABG – coronary artery bypass grafting (coronary artery bypass grafting under cardiopulmonary bypass; off-pump coronary artery bypass grafting without cardiopulmonary bypass; robot-assisted coronary artery bypass grafting; coronary artery bypass grafting with heart valve replacement under cardiopulmonary bypass; coronary artery bypass grafting with heart valve repair under cardiopulmonary bypass; coronary artery bypass grafting with heart valve replacement and repair under cardiopulmonary bypass; coronary artery bypass grafting combined with transmyocardial laser revascularization of the heart; coronary artery bypass grafting combined with transmyocardial laser revascularization of the heart under cardiopulmonary bypass)

HDL – high-density lipoproteins

LV – left ventricle

LDL – low-density lipoproteins

LBBB – left bundle branch block

IU – international units

IVS – interventricular septum

INR – international normalized ratio

MRI – magnetic resonance imaging (magnetic resonance imaging of the heart and great vessels; magnetic resonance imaging of the heart with contrast enhancement)

UFH – unfractionated heparin (syn.: sodium heparin**)

ACS – acute coronary syndrome

NSTE-ACS – non-ST-segment elevation acute coronary syndrome

STEMI – ST-segment elevation acute coronary syndrome

OCT – optical coherence tomography

CVA – cerebrovascular accident

PVR – peripheral vascular resistance

ICU – intensive care unit

AHF – acute heart failure

РКИ – randomized controlled trial

eGFR – estimated glomerular filtration rate

RF – Russian Federation

Endovasc – endovascular diagnostic and treatment methods

BMS – bare-metal stent (syn.: uncoated metal coronary artery stent***)

DES – drug-eluting stent (fully bioresorbable drug-eluting coronary artery stent***; drug-eluting coronary artery stent with a bioresorbable polymer coating***; drug-eluting coronary artery stent with a non-bioresorbable polymer coating***)

DM – diabetes mellitus

CI – cardiac index

syn.: – synonym

DVT – deep vein thrombosis

TIA – transient ischemic attack

PE – pulmonary embolism

LVT – thrombolytic therapy (syn.: intravenous administration of medicinal products for thrombolytic therapy)

AFL – atrial flutter

LCE – level of confidence of evidence

US – ultrasound examination

GRS – grade of recommendation strength

EF – ejection fraction

VF – ventricular fibrillation

FC – functional class

FFR – fractional flow reserve

AF – atrial fibrillation

CKD – chronic kidney disease

Chol – cholesterol

LDL-C – low-density lipoprotein cholesterol

CHF – chronic heart failure

CVP – central venous pressure

PCI – percutaneous coronary intervention (transluminal balloon coronary angioplasty; coronary artery stenting; transluminal balloon angioplasty and stenting of coronary arteries; retrograde coronary artery recanalization with stenting; antegrade coronary artery recanalization with stenting; thrombectomy from a vascular graft (coronary); embolectomy (from a coronary artery); attempted coronary artery stenting)

HR – heart rate

ECG – electrocardiography (syn.: recording of the electrocardiogram), electrocardiogram

ECMO – extracorporeal membrane oxygenation

PM*** – pacemaker (dual-chamber implantable pacemaker, without rate response***; dual-chamber implantable pacemaker, rate-responsive***; single-chamber implantable pacemaker, without rate response***; single-chamber implantable pacemaker, rate-responsive***; triple-chamber (biventricular) implantable pacemaker***; dual-chamber implantable pacemaker, rate-responsive, magnetic resonance imaging-conditional***)

EchoCG – echocardiography

ARC-HBR – Academic Research Consortium for High Bleeding Risk

NYHA – New York Heart Association

PCSK9 – proprotein convertase subtilisin/kexin type 9

POC – point of care

SpO₂ – blood oxygen saturation level determined by pulse oximetry

Terms and Definitions

Evidence-based medicine – the conscientious, explicit, and judicious use of current best evidence (clinical research results) in making decisions about the care and treatment of individual patients [1, 2].

Disease – a disorder of body function, working capacity, and the ability to adapt to changing environmental and internal conditions arising from the impact of pathogenic factors, accompanied by simultaneous alterations in the body's protective-compensatory and protective-adaptive reactions and mechanisms [1].

Instrumental diagnostics – diagnostics using various devices, apparatus, and instruments.

Non-ST-segment elevation myocardial infarction (NSTEMI) – myocardial infarction in which, in the early stages of the disease, the ECG shows no persistent (lasting more than 20 minutes) ST-segment elevation in at least two contiguous leads and no newly developed left bundle branch block.

Outcome – any possible result arising from exposure to a causal factor, preventive or therapeutic intervention, or all established changes in health status resulting from an intervention [3].

Conflict of interest – a situation where a medical or pharmaceutical worker, in the exercise of their professional activities, has a personal interest—either directly or through a representative of a company—in obtaining material gain or other advantage that affects or may affect the proper performance of their professional duties due to a contradiction between the personal interest of the medical or pharmaceutical worker and the interests of the patient [1].

Clinical trial – any investigation involving human subjects intended to discover or verify the clinical and/or pharmacological effects of investigational products, and/or to identify any adverse reactions to investigational products, and/or to study their absorption, distribution, metabolism, and excretion in order to ascertain their safety and/or efficacy. The terms "clinical trial" and "clinical study" are synonymous [2, 3].

Laboratory diagnostics – a set of methods aimed at analyzing test material using various specialized equipment.

Medicinal products – pharmacological agents in dosage forms used for the prevention, diagnosis, and treatment of diseases, rehabilitation, as well as for the preservation, prevention, or termination of pregnancy [4].

Medical intervention – types of medical examinations and/or medical procedures, as well as artificial termination of pregnancy, performed by a medical worker or other employee authorized to engage in medical activities in relation to a patient, affecting the physical or mental state of a person and having a preventive, diagnostic, therapeutic, rehabilitative, or research focus [1].

Medical worker – an individual who has a medical or other education, works in a medical organization, and whose job (official) duties include the implementation of medical activities, or an individual who is an individual entrepreneur directly engaged in medical activities [1].

Mechanical heart valve prosthesis – mechanical bileaflet aortic valve prosthesis***; mechanical bileaflet mitral valve prosthesis***; mechanical bileaflet aortic valve prosthesis combined with a biological polymer aortic graft***.

Non-invasive stress tests – exercise electrocardiography, pharmacologically induced electrocardiography, exercise echocardiography, pharmacological stress echocardiography, myocardial scintigraphy with functional tests, myocardial perfusion single-photon emission computed tomography with functional tests.

Coronary artery bypass grafting (CABG) surgery – creation of a bypass graft to improve blood flow distal to a hemodynamically significant coronary artery stenosis. Depending on the technique, it includes aortocoronary, mammarocoronary, and other types of bypass grafting.

Acute myocardial injury – an increase and/or decrease in blood cardiac troponin concentration where at least one value exceeds the 99th percentile of the upper reference limit in patients without a baseline elevation in cardiac troponin, or an increase of > 20% if baseline cardiac troponin is elevated and previously stable (variability ≤ 20%) or decreasing [5].

Acute myocardial infarction (MI) – acute myocardial injury due to ischemia [5].

Acute coronary syndrome (ACS) – a term used to describe any group of clinical signs or symptoms compatible with acute myocardial infarction or unstable angina.

ST-segment elevation myocardial infarction (STEMI) — newly developed clinical signs or symptoms of myocardial ischemia combined with persistent (lasting more than 20 minutes) ST-segment elevation in at least two contiguous ECG leads.

Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) – newly developed clinical signs or symptoms of myocardial ischemia when the ECG shows no persistent (lasting more than 20 minutes) ST-segment elevation in at least two contiguous leads and no newly developed left bundle branch block.

Patient – an individual who receives medical care or applies for medical care regardless of the presence of a disease and their condition [1].

Post-infarction angina – angina pectoris that occurs within the first 2 weeks from the onset of myocardial infarction.

Working Group for the Development / Updating of Clinical Guidelines – a team of specialists working together and in coordination to develop / update clinical guidelines and bearing joint responsibility for the results of this work.

Revascularization - performance of procedures included in the concepts of PCI and/or CABG, in any combinations.

Resynchronization therapy - implantation of a special biventricular (three-chamber) pacemaker for cardiac resynchronization (implantable three-chamber (biventricular) cardioverter-defibrillator (CRT-D); implantable three-chamber (biventricular) pacemaker***, implantable three-chamber (biventricular) pacemaker, MRI compatible*** (CRT-P)).

Symptom – a sign of a disease, a statistically significant deviation of an indicator from its normal limits, or the occurrence of a qualitatively new phenomenon uncharacteristic of a healthy body.

Syndrome – a stable set of several symptoms with a single pathogenesis.

Condition – changes in the body arising due to the impact of pathogenic and (and/or) physiological factors and requiring medical care [3].

Bare-metal stent (BMS) – an uncovered metal coronary stent; it is a metal framework made of a biologically inert material.

Drug-eluting stent (DES) – a coronary stent*** from the structures of which an antiproliferative substance is released for a certain time after placement, preventing neointimal hyperplasia and thereby helping to prevent restenosis.

Thesis-recommendation – a statement reflecting the procedure and correctness of performing a particular medical intervention with proven efficacy and safety.

Level of Evidence (LoE) – the degree of certainty that the found effect of a medical intervention is true [3].

Grade of Recommendation (GoR) – the degree of certainty in the validity of the intervention effect and that following the recommendations will bring more benefit than harm in a particular situation [3].

Surgical treatment – a method of treating diseases by dividing and uniting tissues during a surgical operation.

Percutaneous coronary intervention (PCI) – restoration of blood flow in a stenosed segment of a coronary artery (CA) using percutaneous introduction of the necessary devices.

Staged revascularization – sequential (i.e., not simultaneous with the revascularization of the culprit CA segment responsible for the given STEMI) performance of procedures included in the concepts of PCI and/or CABG, in any combinations, during or after the index hospitalization in order to achieve complete or maximally possible revascularization of the coronary bed.

CHA₂DS₂-VASc – risk score for ischemic stroke in atrial fibrillation in patients without a mechanical heart valve prosthesis and moderate / severe mitral stenosis.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Acute coronary syndrome (ACS) — a term denoting any group of clinical signs or symptoms allowing suspicion of myocardial infarction (MI) or unstable angina (UA). The term "ACS" is used when diagnostic criteria for a nosological diagnosis ("MI" or "UA") are insufficient and, therefore, represents a provisional diagnosis in the first hours and days of the disease, whereas the terms "MI" and "UA" are used when formulating the final diagnosis. Accordingly, the term "ACS" can be used at the pre-hospital or early hospital stages and is subsequently transformed into a diagnosis of "acute MI", "UA", or, based on the results of differential diagnosis, into any other diagnosis, including non-cardiac.

ACS can be either a manifestation of the destabilization of chronic coronary artery disease (CAD) or the first manifestation of coronary artery disease in patients who have not previously presented with any cardiac complaints.

Acute coronary syndrome with persistent ST-segment elevation on the electrocardiogram (STEMI) — newly developed clinical signs or symptoms of myocardial ischemia combined with the presence of persistent (lasting more than 20 minutes) ST-segment elevation in at least two contiguous electrocardiogram (ECG) leads or newly developed left bundle branch block (LBBB).

MI – acute myocardial injury due to ischemia. To diagnose acute MI not related to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), an increase and/or decrease in blood cardiac troponin concentration should be documented, which must exceed the 99th percentile of the upper reference limit at least once in patients without a baseline elevation of blood cardiac troponin, or an increase and/or decrease in cardiac troponin concentration > 20% if baseline levels are initially stably (variability was ≤ 20%) elevated, combined with at least one criterion of acute myocardial ischemia.

Criteria for myocardial ischemia:

newly developed (или presumably newly developed) ischemic changes on the ECG;
appearance of pathological Q waves on the ECG;
imaging evidence of new areas of viable myocardium loss or regional wall motion abnormalities consistent with an ischemic etiology;
detection of intracoronary thrombosis by coronary angiography (CAG) or autopsy.

More detailed criteria for myocardial infarction are presented in Appendix A3. Criteria for the diagnosis of myocardial infarction [5].

ECG changes characteristic of myocardial ischemia:

Newly developed ST-segment elevations at the J point in at least two contiguous ECG leads ≥ 0.1 mV in all leads except leads V₂–V₃, where ST-segment elevation should be ≥ 0.2 mV in men aged 40 years and older, ≥ 0.25 mV in men younger than 40 years, or ≥ 0.15 mV in women (in the absence of left ventricular (LV) hypertrophy or LBBB).
Newly developed horizontal or downsloping ST-segment depressions ≥ 0.05 mV in at least two contiguous ECG leads and/xlr T-wave inversions > 0.1 mV in at least two contiguous ECG leads with a dominant R wave or an R/S amplitude ratio > 1 [5].

ST-segment elevation myocardial infarction (STEMI) — MI characterized by persistent (lasting more than 20 minutes) ST-segment elevation in at least two contiguous ECG leads in the early stages of the disease. Patients with newly developed LBBB are also included in this category.

It is implied that in the vast majority of cases, such ECG changes are caused by transmural ischemic myocardial injury due to acute complete occlusion of a major CA branch. In the absence of revascularization (interventional, surgical, medical, or spontaneous), a necrosis of a fairly large area of the heart muscle, usually transmural, subsequently develops. Transmural injury and, subsequently, transmural myocardial necrosis are associated with a very high risk of death from fatal heart rhythm and conduction disturbances, myocardial rupture, and acute heart failure (AHF).

Post-infarction angina — angina pectoris occurring within the first 2 weeks from the onset of myocardial infarction.

Due to the fact that "myocardial infarction" is a nosological diagnosis (cannot be established prior to an increase in cardiac troponins proven by laboratory methods), and medical care must be provided before its verification (provided that a provisional diagnosis of "ACS" and its type according to ECG ST-segment displacement has been established), the recommendations given in this document are valid for both the diagnosis of "STEMI" and the diagnosis of "STEMI ACS".

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

MI is generally a consequence of large coronary artery (syn.: epicardial artery) atherothrombosis. A thrombus most frequently forms at the site of a ruptured fibrous cap of a so-called "vulnerable" (unstable) atherosclerotic plaque (AP)—characterized by a large lipid core, rich inflammatory infiltrate, and a thinned fibrous cap; however, an occlusive thrombus may also develop at a site of coronary endothelial defect (erosion) not necessarily localized on the AP surface. Occlusion frequently develops at the site of a hemodynamically insignificant coronary stenosis. Unlike NSTE-ACS, the pathogenesis of which is based on non-occlusive mural thrombosis, STEMI is almost invariably characterized by complete and persistent thrombotic occlusion of a major epicardial artery, leading to transmural myocardial ischemia / injury / necrosis.

Multiple "vulnerable" APs, including those with disrupted surface integrity, are frequently found in the coronary arteries of patients with STEMI. Due to the high risk of recurrent coronary occlusions, such patients require a combination of local interventions (targeting the specific AP responsible for the clinical presentation of MI) and systemic therapeutic measures aimed at reducing the likelihood of injury to other APs and the formation of atherothrombosis.

A thrombus located on the surface or even within the structures of an AP can be a source of embolization into the distal coronary vascular bed. Microvascular myocardial embolization can independently lead to the formation of small foci of necrosis and/or contribute to the expansion of the primary necrotic zone. Furthermore, in the event of large coronary artery occlusion resolution, small thromboembolism can impair blood flow at the microcirculatory level, preventing the full restoration of myocardial blood supply (reperfusion).

Myocardial ischemia may be provoked or exacerbated by anemia, hypoxemia, inflammation, infection, fever, as well as metabolic or endocrine disorders (particularly hyperthyroidism). Coronary spasm, dissection, and thrombosis, alongside tachycardia and elevated blood pressure (BP), can occur with the use of cocaine and certain other substances.

In the majority of patients with STEMI, even with the timely administration of treatment (reperfusion), myocardial necrosis of varying—and in most cases significant—extent develops. The amount of dying and necrotic myocardium is nearly linearly related to the risk of cardiac arrest caused by asystole or fatal ventricular arrhythmias, primarily ventricular fibrillation. The area and depth of myocardial necrosis determine the risk of developing yet another potentially fatal complication of STEMI—myocardial rupture.

The consequence of losing a substantial portion of active myocardium is the process of cardiac remodeling. The formation of necrotic foci in the myocardium is accompanied by changes in the size, shape, and wall thickness of the LV, while the surviving myocardium experiences increased load and undergoes hypertrophy. The pumping function of the structurally and geometrically altered LV deteriorates, leading to heart failure. The most unfavorable manifestation of LV remodeling in MI is considered to be the formation of an LV aneurysm, almost always associated with overt heart failure, and occasionally with intracavitary thrombus formation posing a severe risk of systemic arterial embolism.

1.3 Epidemiology of the Disease or Condition

Circulatory system diseases (CSD) are the leading cause of death among the adult population of the Russian Federation (RF). In recent years, the share of CSD in the structure of mortality causes has exceeded 40%: 2019 — 46%, 2020 — 45%, 2021 — 38% (decrease due to a large share of COVID-19 infection — 17%), 2022 — 44% of the total number of deaths. In the structure of CSD mortality, IHD accounted for 42.3% in 2022. Approximately the same contribution of IHD to CSD mortality is recorded in most countries and regions [6]. In the same year, MI as a cause of death was registered in 48,911 individuals (5.9% in the structure of CSD mortality) [7].

According to the monitoring data of the Ministry of Health, 438,315 cases of ACS were registered in the RF in 2022 (12.5% fewer than in 2021), including 150,845 cases of STEMI. A diagnosis of acute MI (including subsequent MI) was established in 219,240 patients, of whom 23,797 died during hospitalization, i.e., 10.9%. There is a positive trend in reducing in-hospital mortality—this same indicator was 17.7% in 2018. According to national registries in Europe, in-hospital mortality ranges from 4 to 12%. Overall in-hospital mortality from ACS in the RF in 2022 was 5.6%. In recent years, the ratio between STEMI and NSTEMI has been steadily shifting toward an increasing proportion of NSTEMI [8], primarily due to the laboratory detection of "additional" NSTEMI cases among those that until recently were classified as UA. An objective prerequisite for this has been the widespread use of cardiac troponins, including high-sensitivity assays, to confirm acute myocardial injury.

Over the past 20 years, there has been a steady increase in the frequency of reperfusion therapy in STEMI. In 2022, primary PCI was performed in 70.9% of cases in the RF, and in major cities, particularly in Moscow, its frequency exceeded 90%. Thrombolytic therapy (TLT) was administered to 22.8% of patients, 73% of whom received it in the pre-hospital setting. Important data on the characteristics of MI reperfusion therapy were obtained from the REGION-MI registry study, which has been conducted since 2020 in more than 40 constituent entities of the RF. Reperfusion therapy (PCI ± TLT) was performed in 88.9% of STEMI patients, and primary PCI in 60.6% of patients. The mean time from symptom onset to primary PCI was 657.4 ± 867.7 min (median — 315 minutes). The mean time from ECG to primary PCI was 138 ± 124.3 min (median — 110 min). Isolated TLT was performed in 7.4%, and a pharmacoinvasive treatment strategy was used in only 20.9% of cases, i.e., in 73% of patients among those who underwent TLT. Thus, despite the high frequency of coronary blood flow restoration, treatment is often administered at late stages, which significantly reduces its efficacy [9].

Despite evident progress in the treatment of ACS, the mid-term and long-term prognosis remains generally unfavorable. According to observational studies, the incidence of major adverse cardiovascular events (cardiovascular death, recurrent MI, ischemic stroke) after MI is approximately 20% [10]. Over the subsequent 3 years, major cardiovascular events are observed in another 20% of patients [11]. Consequently, post-MI patients belong to the very high-risk category for complications, which necessitates clinical follow-up and the implementation of effective secondary prevention, both pharmacological and non-pharmacological.

1.4 Features of Coding the Disease or Condition

I21 Acute myocardial infarction

I21.0 Acute transmural myocardial infarction of anterior wall

I21.1 Acute transmural myocardial infarction of inferior wall

I21.2 Acute transmural myocardial infarction of other specified sites

I21.3 Acute transmural myocardial infarction of unspecified site

I21.9 Acute myocardial infarction, unspecified

I22 Subsequent myocardial infarction

I22.0 Subsequent myocardial infarction of anterior wall

I22.1 Subsequent myocardial infarction of inferior wall

I22.8 Subsequent myocardial infarction of other specified sites

I22.9 Subsequent myocardial infarction of unspecified site

I24 Other acute ischemic heart diseases

I24.0 Coronary thrombosis not resulting in myocardial infarction

I24.8 Other forms of acute ischemic heart disease

I24.9 Acute ischemic heart disease, unspecified

Most frequently, the outcome of STEMI is an MI with Q-wave formation on the ECG. In such cases, codes I21.0–I21.2 and I22.0–I22.8 are assigned. If STEMI leads to an MI without Q-wave formation, codes I21.0–I21.2 and I22.0–I22.8 are likewise assigned.

In cases where ST-segment elevation ACS progresses to STEMI (with Q-wave formation), codes I21.0–I21.2 and I22.0–I22.8 are assigned.

In cases where STEMI does not result in MI (criteria for MI are absent), including instances of effective invasive / pharmacological reperfusion or spontaneous reperfusion, code I24.0 is assigned. Recommended formulation: "Acute coronary thrombosis without development of MI (must specify — secondary to TLT, PCI or TLT and PCI)".

In cases of sudden death in a patient with STEMI (Type 3 MI according to the 4th Universal Definition criteria), the clinical diagnosis should utilize category I24.8 (recommended formulation: "Sudden coronary death").

So-called "unspecified" categories (I21.3, I21.9, I22.9, I24.9) and their corresponding formulations in the final clinical diagnosis may be used only in exceptional cases—when objective diagnostic difficulties exist. They must not be used in pathoanatomical and forensic autopsy diagnoses.

The use of codes from Section I23 "Certain current complications following acute myocardial infarction" when coding the underlying disease / initial cause of death is unacceptable (these conditions are complications of the underlying disease — MI).

After 28 days from the onset of STEMI symptoms, the diagnosis of "MI" is no longer used. In such cases, it is customary to indicate a prior MI, designating this condition as "Post-infarction cardiosclerosis".

1.5 Classification of the disease or condition

Classifications of ACS and acute MI:

At the preliminary diagnosis stage:

STEMI — ST-elevation myocardial infarction (this wording is also used for ACS / MI with newly onset LBBB);
Non-ST-elevation ACS (not covered in this document).

Clinical diagnosis (including final diagnosis) after confirmation / exclusion of MI:

ST-elevation myocardial infarction (this wording is also used for MI with newly onset LBBB);
Non-ST-elevation myocardial infarction (not covered in this document);
Unstable angina (not covered in this document).

MI classification based on subsequent ECG changes (optional):

MI with the development of pathological Q waves;
MI without the development of pathological Q waves.

MI classification based on the depth of myocardial layer involvement (this is the priority for autopsy / forensic medical diagnosis):

Subendocardial MI;
Transmural MI.

MI classification based on the localization of the acute ischemic injury / necrosis focus:

Left ventricular anterior wall MI (anterior MI);
Left ventricular lateral wall MI (lateral MI);
MI of the cardiac apex;
Left ventricular inferior wall MI (inferior MI);
LV posterior wall MI (posterior MI);
Interventricular septum MI;
Right ventricular MI;
Atrial MI;
Combined localizations are possible: posteroinferior, anterolateral, etc.

MI classification based on the history of prior MI:

Recurrent MI — an MI developing after 28 days from the onset of a previous MI;
Reinfarction — an MI developing within 28 days (inclusive) from the onset of a previous MI.

Classification of MI types [5]:

Type 1. MI caused by atherosclerotic plaque rupture or erosion in a coronary artery with subsequent intracoronary thrombus formation (atherothrombosis), leading to a sharp decrease in blood flow distal to the damaged plaque or distal embolization by thrombotic masses / plaque fragments, followed by myocardial necrosis. A rarer cause of type 1 MI is an intramural hematoma within the damaged plaque with a rapid increase in its volume and narrowing of the arterial lumen.

Type 2. MI resulting from ischemia caused by conditions unrelated to thrombotic complications of coronary atherosclerosis. Pathophysiologically, such myocardial infarctions are associated with an increased myocardial oxygen demand and/or decreased myocardial oxygen delivery, for example, due to coronary artery embolism, spontaneous coronary artery dissection, respiratory failure, anemia, cardiac arrhythmias, arterial hypertension (AH) or hypotension, etc. Type 2 MI can occur in patients both with and without coronary atherosclerosis.

Type 3. Type 3 MI refers to cases with symptoms suggestive of myocardial ischemia, accompanied by presumed new ischemic ECG changes or ventricular fibrillation, where patients die before blood samples can be obtained or before the activity of myocardial necrosis biochemical markers in the blood increases. The diagnosis is confirmed based on the detection of acute MI at autopsy.

Type 4a. MI associated with complications occurring during the PCI procedure and within the first 48 hours thereafter.

Type 4b. MI associated with coronary stent thrombosis, documented by angiography or autopsy. Depending on the time elapsed after stent implantation, acute (0–24 h), subacute (>24 h – 30 days), late (>30 days – 1 year), and very late (>1 year) stent thrombosis are distinguished.

Type 4c. MI associated with restenosis following PCI. Type 4c MI is diagnosed when significant restenosis is detected in the artery corresponding to the infarct zone in the absence of thrombosis and other lesions of the culprit artery.

Type 5. MI associated with coronary artery bypass graft (CABG) surgery.

Diagnostic and differential diagnostic criteria for various types of MI are presented in Appendix A3. Diagnostic criteria for myocardial infarction [5, 12, 13].

1.6 Clinical presentation of the disease or condition

Myocardial ischemia / injury / necrosis is characterized by retrosternal pain, tightness, pressure, or heaviness, which patients sometimes describe as discomfort. Radiation to the left arm, left shoulder, throat, lower jaw, and epigastrium is possible, as well as atypical clinical manifestations such as sweating, nausea, abdominal pain, shortness of breath, asphyxia, and loss of syncope, which in some cases are the only or predominant symptoms.

In MI, symptoms are similar in nature to those occurring during an anginal attack, but differ in intensity and duration (more severe and prolonged). Furthermore, in MI, symptoms typically occur at rest and are not relieved by nitroglycerin**, and sometimes even by repeated narcotic analgesic injections. The intensity of pain can vary from mild to unbearable; symptoms may wax and wane and last from 20 minutes to several hours. In cases of atypical clinical presentations, depending on the predominant symptoms, patients with developing MI can present with asthmatic, abdominal, arrhythmic, cerebrovascular variants, as well as a paucisymptomatic (silent) form.

The clinical presentation of STEMI may include, and sometimes be dominated by, symptoms of its major complications — acute heart failure (pulmonary edema, cardiogenic shock), severe bradycardia, or tachycardia. One of the possible clinical manifestations of MI, sometimes the only one available for physician assessment, may be a constellation of symptoms characteristic of cardiac arrest caused by ventricular tachycardia / ventricular fibrillation, asystole, or electromechanical dissociation. In patients with reversed or spontaneously resolved cardiac arrest, the leading symptom may be varying degrees of persistent impaired consciousness, up to deep coma.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria — see Appendix A3 Diagnostic criteria for myocardial infarction.

2.1 Complaints and Anamnesis

In the initial diagnosis of STEMI, it is recommended to rely on assessing the nature of the pain syndrome and/or its equivalents. Radiation of pain to the neck, lower jaw, and left arm is quite typical. However, in some patients, less characteristic symptoms may come to the forefront — shortness of breath, epigastric pain, nausea, dizziness, weakness, and others. A positive effect of nitroglycerin** does not rule out STEMI.

Upon initial medical contact with a patient, it is recommended to rely on the clinical manifestations of the disease, ECG changes, and to record the time from the onset of the pain episode to contact with a physician (medical worker). The latter is important for making key management decisions for a STEMI patient. In certain cases of differential diagnosis with other conditions / diseases accompanied by ST-segment elevation on the ECG, one should focus on a detailed study of the characteristics of the pain syndrome, as well as data from other diagnostic modalities, primarily imaging (e.g., echocardiography (EchoCG), multislice computed tomography) and laboratory tests.

In all patients with suspected STEMI, it is recommended to collect and evaluate complaints and medical history to determine the specific features of CHD exacerbation, perform differential diagnosis, identify symptoms that allow assessment of the presence and severity of other diseases that provoke or complicate the course of STEMI and may influence the choice of treatment approaches, as well as to detect STEMI complications [14].

ESC IC (LoE C, SoR 5)

Comments: Clinical manifestations of STEMI are diverse — ranging from cardiac arrest, shock, and life-threatening arrhythmias to minimal complaints of mild retrosternal discomfort/shortness of breath, and in some cases, the complete absence of clinical symptoms.

Chest pain and cardiac discomfort, apart from heart diseases, may be caused by pathologies of other thoracic organs (lungs, pleura, mediastinum, diaphragm), the digestive tract, chest wall musculoskeletal structures, nervous system disorders, and psychogenic conditions.

At the initial diagnostic stage, it is recommended to rely on clinical manifestations (features of the pain syndrome and less characteristic symptoms and signs potentially associated with acute myocardial ischemia), medical history data, the presence of CHD risk factors, the nature of ECG changes, in some cases — data on regional left ventricular contractility, as well as the assessment of time from the last pain episode to medical contact. Whenever possible, ECGs recorded during and outside of transient symptoms and signs potentially related to myocardial ischemia, as well as prior to the current deterioration of CHD clinical course, should be compared.

Additional diagnostic methods are required to confirm myocardial ischemia when ECG data are inconclusive, to rule out diseases with similar clinical symptoms, to detect MI, to assess (stratify) the risk of an adverse clinical course, and to identify conditions that influence patient management strategies.

It is recommended to take into account pre-hospital medication use that may affect the management strategy for a patient with STEMI.

2.2 Physical Examination

Physical examination does not provide direct information on the criteria for ACS or STEMI, but it is recommended for the timely detection of STEMI complications (jugular venous distension and wet rales in the lungs in heart failure, auscultatory murmurs in ventricular septal rupture or mitral regurgitation) as well as other causes of symptoms (pericardial friction rub in pericarditis, asymmetrical pulses in aortic aneurysm, percussion and auscultation signs of air in the pleural cavity in pneumothorax, etc.), i.e., for differential diagnosis [14].

ESC 1C (LoE C, GoR 5)

2.3 Laboratory Diagnostics

In patients with STEMI, to confirm the diagnosis of STEMI, it is recommended to test for cardiac troponin T or I levels (according to the nomenclature of medical services: blood testing for troponins I and T; if unavailable, rapid testing for blood troponins I and T) [14-17].

ESC 1B (LoE A, GoR 1)

Comments: Regarding STEMI, laboratory confirmation of acute myocardial injury using cardiac troponin assays is of a formal nature and has secondary importance, since the patient management strategy is based on the clinical presentation and ECG (i.e., all major decisions regarding the care of a patient with STEMI do not depend on laboratory confirmation of STEMI). Moreover, crucial decisions, such as the administration of a thrombolytic agent or primary PCI, should not be delayed until troponin test results are available. Determination of markers of acute myocardial injury is necessary to confirm the nosological diagnosis of STEMI.

It is recommended to use quantitative (not qualitative or semi-quantitative) determination of cardiac troponin levels. Qualitative and semi-quantitative methods do not allow for the assessment of changes in the concentration of these markers, which is necessary for establishing the nosological diagnosis (STEMI).

High-sensitivity assay methods (i.e., those capable of detecting cardiac troponin in ~50–95% of healthy individuals) performed on automated analyzers provide higher diagnostic accuracy compared to point-of-care (POC) testing formats. Most POC tests cannot be considered high-sensitivity, demonstrating lower diagnostic accuracy and negative predictive value. However, they have the advantage of rapid result turnaround. A randomized trial involving low-risk patients with suspected acute MI and symptom onset ≥ 2 hours before calling an ambulance showed that using a pre-hospital acute MI exclusion strategy (single standard POC troponin measurement) resulted in a significant reduction in 30-day treatment costs and had a comparable incidence of major adverse cardiovascular events when compared to the exclusion strategy using the standard emergency department protocol [18].

In general, automated high-sensitivity troponin assays are preferred; however, the rapidly developing POC testing system will soon force a reassessment of this preference once more thoroughly validated high-sensitivity POC tests become clinically available [14].

A transient increase in blood cardiac troponin levels indicates acute myocardial injury regardless of the cause, which may be associated with primary coronary blood flow restriction as well as other factors, including non-cardiac ones (Appendix A3. Causes of elevated blood cardiac troponin concentration). An increase and/or decrease in the concentration of cardiac troponin above the 99th percentile of the upper reference limit in individuals without an initial baseline elevation, or a cardiac troponin concentration increase > 20% when previously stably elevated (variability was ≤ 20%) in the presence of myocardial ischemia criteria indicates acute MI (Appendix A3. Causes of elevated blood cardiac troponin concentration).

Assessment of cardiac troponin levels is considered a more sensitive and specific method than determining the MB fraction of creatine kinase or myoglobin. The latter is not recommended for use as it is not a cardiospecific marker.

In all patients with suspected STEMI, it is recommended to perform a complete blood count (CBC), a general systemic blood chemistry panel (total protein, urea, total bilirubin, blood aspartate aminotransferase and alanine aminotransferase activities), and a routine urinalysis as part of the initial evaluation upon hospital admission and, if necessary, for subsequent follow-up monitoring during hospitalization [19-22].

ESC 1C (LoE C, GoR 4)

Comment: In all patients with suspected STEMI upon hospital admission, a complete blood count with assessment of total hemoglobin, hematocrit, erythrocyte, and platelet levels is recommended. Detection of decreased total hemoglobin, erythrocytes, and/or platelets in the blood is a sign of increased hemorrhagic risk; a high platelet count increases the risk of early stent thrombosis. During hospitalization, laboratory tests should be repeated if clinically indicated.

In all patients with suspected STEMI, to assess the risk of ischemic and hemorrhagic events and to ensure treatment safety, it is recommended to test blood creatinine levels upon hospital admission and subsequently when clinically indicated, with calculation of the estimated glomerular filtration rate, and in case of direct oral anticoagulant prescription, also creatinine clearance (CrCl) [23, 24].

ESC IA (LoE A, GoR 3)

Comment: Blood creatinine levels and the calculated indicator of renal filtration function are important for selecting the dose of a number of drugs (the choice of renal function criterion is determined by the drug's Instructions for Use). The estimated glomerular filtration rate (eGFR) is used in the diagnosis of chronic kidney disease (CKD) and is important for assessing the risk of ischemic and hemorrhagic events.

In all patients with suspected STEMI, it is recommended to test fasting blood glucose levels, screen for diabetes mellitus (DM) (glucose metabolism testing; oral glucose tolerance test; blood glycated hemoglobin testing), and repeat blood glucose testing in patients with a history of DM or hyperglycemia upon admission in order to assess the risk of an adverse outcome [25-30].

ESC IIaB (Level of Evidence B, Grade of Recommendation 3)

Comment: Blood glucose levels are also important for determining the need for glucose-lowering medications and selecting their doses. During hospitalization, blood glucose concentrations should be reassessed when clinically indicated.

In patients with STEMI, it is recommended as soon as possible after admission, preferably within the first 24 hours, to perform a biochemical blood test to assess lipid metabolism disorders (blood total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels) for subsequent comparison with lipid levels achieved using lipid-lowering drugs [31-33].

ESC IC (LoE C, GoR 5)

Comment: It is necessary to determine at least total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.

In all patients with STEMI, to ensure treatment safety, it is recommended to determine blood electrolyte levels (minimally — blood potassium and sodium levels; optimally — blood potassium, sodium, and serum total magnesium levels) and, if clinically indicated, assess acid-base balance and blood gases with correction and re-evaluation in case of deviations from normal values [34, 506, 507].

ESC IIbC (LoE C, GoR 4)

Comment: During hospitalization, blood electrolyte concentrations should be re-evaluated when clinically indicated.

All patients with STEMI admitted to the hospital are recommended to undergo a coagulogram (aPTT, prothrombin time, prothrombin index, fibrinogen), determination of the international normalized ratio (INR) if taking warfarin, as well as determination of the Rh factor, ABO blood group system, Rhesus D antigen (Rh factor), and phenotypeing for C, c, E, e, Cw, K, and k antigens to predict the risk of perioperative bleeding and blood loss volume. Determination of hepatitis B virus surface antigen (HBsAg) in the blood, determination of antibodies to hepatitis C virus in the blood, determination of antibodies to Treponema pallidum in the blood, determination of IgM and IgG antibodies to human immunodeficiency virus HIV-1 in the blood, and determination of IgM and IgG antibodies to human immunodeficiency virus HIV-2 in the blood are recommended for all STEMI patients to rule out association with HIV infection and hepatitis [14, 538–546].

RSC 1C (Level of Evidence C, Grade of Recommendation 4)

2.4 Instrumental Diagnostics

Within 10 min from the start of initial medical contact with a patient with suspected ACS, to determine the ACS type and perform differential diagnosis with other diseases, it is recommended to record an ECG at the site of initial contact and interpret the electrocardiographic data by a qualified specialist (healthcare professional) [5, 35, 36, 508].

ESC IB (Level of Evidence C, Grade of Recommendation 5)

Comment: If the healthcare personnel at the initial medical contact encounter difficulties in interpreting the ECG at the site of recording, it is recommended to perform decoding, description, and interpretation of the ECG data using telemedicine technologies. Re-recording the ECG at the stage of the first medical contact may be appropriate if the nature of the pain syndrome or ACS clinical presentation changes.

In all patients with suspected STEMI, to determine the ACS type and perform differential diagnosis with other diseases, it is recommended to record a resting ECG in at least 12 standard leads [37–40, 508].

ESC IA (LoE A, GoR 2)

Comment: If the ECG changes in the 12 standard leads are uninformative (no ST-segment shift sufficient for diagnosis), but clinical data suggest the presence of acute myocardial ischemia/injury, it is recommended to use additional leads, such as V₇–V₉ and V₃R–V₄R. When the ECG is uninformative in patients with persistent suspicion of ACS and ongoing or recurring symptoms, to timely detect ischemic changes, it is recommended to re-record the ECG (e.g., at intervals of 15–30 min during the first hour) or initiate 12-lead ST-segment shift monitoring.

It is recommended to use additional ECG leads (V₃R–V₄R and/or V₇–V₉) in patients with inferior LV STEMI and/or suspected right ventricular and/or posterior LV myocardial infarction to diagnose the extension of the infarct zone to the right ventricle and/or posterior LV regions [41–43].

ESC IB (LoE B, LoR 2)

In patients with STEMI, for the timely detection and elimination of cardiac arrhythmias, it is recommended to promptly initiate ECG monitoring (monitoring of electrocardiographic data) [44–47].

ESC IB (Level of Evidence C, Grade of Recommendation 5)

All patients with STEMI admitted within the first 48 hours of disease onset are recommended to undergo electrocardiographic monitoring for at least 24 hours to assess treatment efficacy and timely detect complications [14, 44, 47].

ESC IC (Level of Evidence C, Grade of Recommendation 5)

Comment: The feasibility of longer ECG monitoring, as well as the feasibility and duration of cardiac rhythm monitoring in STEMI patients and those admitted later than 48 hours after disease onset, is determined by the severity of the clinical condition and the risk of life-threatening arrhythmias. STEMI patients at high risk of life-threatening arrhythmias include those with a known history of ventricular arrhythmia prior to MI, late presentation (more than 12 hours from disease onset), low LVEF (≤ 40%), suboptimal reperfusion therapy results, or complications during PCI.

In all patients with STEMI at high risk for ventricular tachycardia (VT) / ventricular fibrillation (VF), it is recommended to perform cardiac rhythm monitoring for more than 24 hours [47].

ESC IC (Level of Evidence C, Grade of Recommendation 5)

Comment: STEMI patients at high risk of life-threatening arrhythmias include those with a known history of ventricular arrhythmia prior to MI, late presentation (more than 12 hours from disease onset), low LVEF (≤ 40%), suboptimal reperfusion therapy results, or complications during PCI.

In patients with NSTE-ACS / STEMI, to resolve the issue of performing PCI, coronary angiography is recommended, mandatory both within the primary PCI strategy and the pharmacoinvasive strategy [48, 49].

ESC IA (LoE A, GoR 2)

Comment: The main objective of coronary angiography is to detect acute occlusion or complicated coronary artery stenosis for subsequent elimination of this lesion via PCI (or bypassing the occlusion site via coronary artery bypass grafting).

All patients with STEMI, to confirm the diagnosis, assess the severity of the lesion, perform differential diagnosis, identify complications, and determine prognosis, are recommended to undergo transthoracic echocardiography (TTE) with mandatory assessment of LVEF, optimally on the first day of hospitalization [14, 50–52, 509].

ESC 1C (LoE C, GoR 5)

Comment: Performing TTE (at least a point-of-care ultrasound examination) should not delay patient transportation for coronary angiography. TTE is necessary to assess LV function and geometry, as well as to recognize complications such as LV mural thrombosis, cardiac rupture, heart valve dysfunction (particularly mitral regurgitation), right ventricular infarction, and pericarditis. If myocardial rupture (external or internal) or ascending aortic dissection is suspected, TTE is recommended as an emergency procedure prior to coronary angiography. Assessing the dynamics of local and global cardiac function helps clarify treatment efficacy. Furthermore, TTE data, primarily LVEF, are essential for determining disease prognosis.

Contrast-enhanced cardiac magnetic resonance imaging (MRI) in STEMI is recommended to be considered as an additional method to clarify the localization and volume of myocardial injury when lesion sizes are relatively small, as well as for differential diagnosis of myocardial lesions, provided technical capabilities are available [53–59].

ESC IIbB (Level of Evidence C, Grade of Recommendation 5)

Comment: Contrast-enhanced cardiac MRI is not recommended as a routine imaging method for STEMI patients. It allows confirmation of a myocardial necrosis focus, differentiation of ischemic vs. inflammatory (myocarditis) etiology of the lesion, and confirmation or exclusion of Takotsubo syndrome, and serves as the reference method for three-dimensional assessment of cardiac chamber morphology and function, as well as the valvular apparatus. An additional advantage of the method is the absence of radiation exposure. However, technical complexities limit its application in the acute phase of the disease. The necessity and feasibility of performing cardiac MRI must not be a reason for delaying coronary angiography.

Cardiac MRI is recommended in cases of inadequate visualization of the LV apex by other methods in patients with a high probability of LV thrombus, provided technical capabilities are available [60, 61].

ESC IIaC (Level of Evidence B, Grade of Recommendation 2)

Computed tomography coronary angiography (CTCA) is not recommended as a routine diagnostic method in STEMI [14, 62–68].

ESC IIIB (Level of Evidence B, Grade of Recommendation 2)

Cardiac computed tomography (CT), chest CT with intravenous bolus contrast enhancement, cardiac ventriculography, myocardial scintigraphy, and aortography (abdominal aortography; panaortography) are not recommended as routine diagnostic methods in STEMI [14, 69, 510, 511].

ESC Not Applicable (Level of Evidence C, Grade of Recommendation 5)

Comment: Examination with intravenous (IV) contrast administration may be useful for differential diagnosis by revealing life-threatening conditions other than MI (aortic dissection, pulmonary embolism (PE), pneumothorax, etc.). In some cases, aortic dissection may be complicated by MI due to involvement of the coronary arteries in the dissection, which can be detected by CTCA or aortography.

2.5 Other Procedures

2.5.1. Risk Stratification for Adverse Outcomes

Despite the availability of numerous risk assessment scales for adverse outcomes (GRACE, TIMI, DYNAMIC TIMI, CADILLAC, PAMI, Zwolle), there are no evidence-based approaches that improve STEMI treatment outcomes through specific in-hospital and post-discharge actions based on risk stratification using these scales. Individual risk of an adverse outcome is determined by the localization and extent of the myocardial infarction (assessed by ECG and echocardiography), the presence of multivascular coronary artery disease, complications of the given myocardial infarction, the timeliness and completeness of myocardial reperfusion, age, and comorbid conditions (primarily impaired renal function and the presence/absence of diabetes mellitus). The fact and success of reperfusion therapy, the presence of sustained ventricular arrhythmias, heart failure, and/or low left ventricular ejection fraction determine the feasibility and timing of implantable cardioverter-defibrillator (ICD) placement.

Routine risk stratification for adverse outcomes using scales in patients with STEMI during hospitalization is not recommended due to the lack of proven effective interventions based on the results of such stratification [14].

ESC IIIC (LoE C, GoR 5)

Comment: In selected patients with STEMI and successful primary PCI, the Zwolle score (Appendix G2) may be considered when deciding on early discharge (within 72 hours of admission) [70, 71].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. Reperfusion Treatment of the Disease

Thrombotic occlusion of a major coronary artery, resulting from atherosclerotic plaque disruption, is a universally recognized primary pathogenetic mechanism of STEMI development. The localization and persistence of the occlusion determine the size of myocardial necrosis, which is directly related to the risk of death from major MI complications (heart failure, potentially fatal rhythm and conduction disturbances, myocardial rupture). Elimination of acute occlusion and restoration of coronary patency (reperfusion) form the basis of treatment for patients with NSTE-ACS / STEMI. Therefore, immediately upon establishing the diagnosis of "STE-ACS", all patients (regardless of age or sex) should be considered candidates for reperfusion therapy. Currently, reperfusion treatment in STE-ACS / STEMI involves two strategies: primary PCI and a pharmacoinvasive approach, which includes sequential thrombolytic therapy and PCI. The choice between these two strategies is determined primarily by the availability of facilities capable of organizing timely PCI.

3.1.1. Selection of Reperfusion Treatment Strategy for the Disease

Reperfusion therapy to reduce the risk of death is recommended for all patients with STEMI and symptom duration < 12 hours [72, 73].

ESC IA (LoE C, GoR 4)

To reduce the risk of death, primary PCI is recommended as the preferred reperfusion strategy within the first 12 hours of STEMI symptom onset, provided the expected time from diagnosis to guidewire crossing in the infarct-related coronary artery does not exceed 120 minutes [73-76].

ESC IA (LoE A, GoR 1)

Comment: Performing primary PCI at a later stage (expected time from diagnosis to guidewire crossing in the infarct-related coronary artery exceeds 120 minutes) leads to a significant increase in mortality, so the recommended algorithm must be strictly followed. In cases of primary PCI, the time interval from diagnosis to coronary guidewire insertion should be met. In a primary PCI-capable center, this time should not exceed 60 minutes, and in patients transferred from "non-invasive" facilities, 90 minutes. Age, impaired renal excretory function, comorbid diseases, and conditions should not be considered limitations/contraindications to primary PCI. Relative contraindications to PCI may include intolerance to radiocontrast agents and extremely high patient body weight (exceeding the limits stated by the angiography system manufacturer). In such cases, bailout thrombolytic therapy without subsequent PCI may be necessary.

A routine primary PCI strategy to reduce the risk of ischemic events is recommended in patients presenting within 12–48 hours of STEMI symptom onset [77-81].

ESC IIaB (LoE B, GoR 2)

In patients with STEMI, regardless of symptom onset time, reperfusion therapy (specifically PCI) is recommended in the event of ongoing ischemia, hemodynamic instability (cardiogenic shock), life-threatening arrhythmias, or cardiac conduction disturbances [82].

ESC I C (LoE C, GoR 4)

If more than 48 hours have elapsed since STEMI onset, routine reperfusion treatment (PCI or CABG) of the infarct-related coronary artery is not recommended in the presence of its complete occlusion and the absence of additional clinical indications for intervention (ongoing or recurrent myocardial ischemia, symptoms of severe heart failure, life-threatening cardiac arrhythmias) [77, 83, 84].

ESC IIIA (LoE A, GoR 2)

Due to the importance of time criteria in choosing a reperfusion treatment strategy in patients with STEMI, it is recommended that all medical facilities providing care to STEMI patients, as well as the emergency medical service, record and monitor compliance with the time intervals specified in this document, both when performing reperfusion therapy and when it is withheld [14].

ESC IC (LoE C, SoR 5)

Emergency medical teams are recommended to be trained in recognizing STEMI-characteristic ECG changes, selecting the reperfusion treatment strategy (pharmacoinvasive approach or transfer to a hospital for primary PCI), determining indications and contraindications for systemic thrombolysis in STEMI, intravenous drug administration techniques for thrombolytic therapy, cardiopulmonary resuscitation, and external defibrillation [14].

ESC IC (LoE C, SoR 5)

3.1.2. Primary Percutaneous Coronary Intervention

When performing primary PCI in patients with STEMI to reduce the risk of death, obligatory intervention on the infarct-related artery is recommended [48, 85].

ESC IA (LoE A, GoR 1)

When performing coronary angiography and PCI in patients with STEMI, radial artery access is recommended as the preferred vascular access to reduce the risk of bleeding, death, major adverse cardiovascular events (MACE), and access-site complications, provided this access route is proficiently mastered at the given institution [86-89].

ESC IA (LoE A, GoR 1)

To reduce the risk of recurrent MI and the need for repeat revascularization in patients with STEMI undergoing primary PCI, transluminal balloon coronary angioplasty with coronary stenting is recommended over isolated transluminal balloon coronary angioplasty (without stenting) [90, 91].

ESC IA (LoE A, GoR 1)

Comment: Meta-analyses have not demonstrated a mortality reduction advantage of coronary stenting over coronary angioplasty. Most of the evidence base indicating the superiority of PCI over thrombolysis in terms of mortality was obtained using balloon angioplasty (without stenting). Therefore, withholding PCI in the form of balloon angioplasty under the pretext of lacking appropriate stents is unjustified.

In special cases of infarct-related coronary artery lesions (coronary embolism, ectatic coronary artery, spontaneous coronary artery dissection, intervention on a previously stented coronary artery segment, diffuse distal coronary artery disease), recanalization may be performed without coronary stenting.

When performing transluminal balloon coronary angioplasty with coronary stenting in patients with STEMI to reduce the risk of recurrent MI, stent thrombosis***, and the need for repeat revascularization, it is recommended to use a new-generation drug-eluting stent (DES)***, regardless of the duration and regimen of planned antiplatelet and anticoagulant therapy [91-95].

ESC IA (LoE A, GoR 1)

Due to the lack of significant impact on the risk of ischemic events and the potential increase in the risk of stroke in patients with STEMI undergoing PCI, it is recommended to refrain from the routine use of manual aspiration thrombectomy (syn.: thrombus aspiration) [96].

ESC IIIA (LoE A, GoR 1)

Comment: The decision to perform thrombus aspiration at the beginning or during the course of PCI can be made based on individual angiographic and clinical patient data.

Invasive functional assessment of the significance of non-infarct-related coronary artery lesions in patients with STEMI during primary PCI is not recommended [97-104].

ESC IIIC (LoE C, GoR 2)

In hemodynamically stable patients with STEMI and multivascular coronary disease, PCI of non-infarct-related coronary arteries with hemodynamically significant stenoses is recommended either during primary PCI or within 45 days after the primary procedure to reduce the composite risk of ischemic events (death, recurrent MI, or repeat revascularization) [105-112].

ESC IA (CURL B, LOR 2)

Comment: The indications for complete revascularization in STEMI are based on the results of several clinical trials, such as PRAMI [105], CvLPRIT [109], DANAMI-3-PRIMULTI [106], COMPARE-ACUTE [110], and COMPLETE [108]. In the latter, among patients with STEMI and multivessel coronary artery disease, staged (second-stage) PCI of non-infarct-related arteries led to a significant reduction in the composite endpoint of adverse events (MI, cardiac death, repeat revascularization) compared to conservative management following primary PCI. Furthermore, in the COMPLETE trial [108], staged PCI was performed both during the index hospitalization and after discharge (within 45 days after primary PCI). When comparing non-infarct-related artery PCI performed during primary PCI versus staged intervention (within 6 days of the index procedure) in the BIOVASC trial [111], both approaches showed comparable mortality outcomes, but the staged revascularization group had a significantly higher incidence of MI and unplanned revascularizations. The benefit of complete revascularization guided by functional stenosis assessment was demonstrated in the FIRE trial [112], where multivessel revascularization in elderly patients showed a significant advantage over revascularization of the infarct-related coronary artery alone.

Measurement of fractional flow reserve (FFR) using hyperemic agents such as #adenosine triphosphate (intravenously (IV) 140 or 180 mcg/kg/min or intracoronary 20 or 40 mcg for a single coronary artery) and #papaverine (intracoronary 12–20 mg for the left coronary artery and 8–20 mg for the right coronary artery) [514–517], and/or instantaneous wave-free ratio, is the standard for assessing the functional significance of borderline (40–90%) coronary artery stenosis.

A stenosis is considered functionally significant with an FFR value ≤ 0.8 and an instantaneous wave-free ratio < 0.89.

Several studies have demonstrated the efficacy of FFR in assessing the functional significance of stenoses in this category of (STEMI) patients as well. The FRAME-AMI trial [104] demonstrated the benefit of FFR in reducing overall mortality, recurrent MI, and unplanned revascularization. Conversely, the FLOWER-MI trial [97] did not demonstrate a benefit of FFR in reducing major adverse cardiovascular events. Additionally, several observational studies have shown that patients with ACS may experience inaccurate functional assessment of lesion severity because microvascular recovery occurs no earlier than 24 hours after symptom onset [98, 99]. Since current trial results are contradictory, the clinical utility of FFR in ACS patients remains a subject of further investigation. Nevertheless, FFR measurement can be used during staged revascularization (within 45 days of STEMI onset) with favorable clinical outcomes, as demonstrated in the FIRE trial [112], where FFR-guided revascularization in elderly patients showed a significant advantage over revascularization of the infarct-related coronary artery alone.

The decision regarding non-infarct-related coronary artery revascularization during primary PCI in patients with STEMI is recommended to be made based on the angiographic severity of the lesion [98, 103, 113].

ESC IB (LoE B, LoR 2)

Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) of the coronary arteries is recommended to be considered as adjunctive tools during PCI in patients with STEMI to improve immediate and long-term procedural outcomes, provided the technical expertise and equipment are available [114–121].

ESC IIaA (LoE A, GoR 2)

Comment: In a number of major meta-analyses and randomized trials, intravascular imaging (IVUS, OCT) has demonstrated a significant impact on long-term outcomes of coronary stenting in terms of preventing stent thrombosis and restenosis. In one of the largest meta-analyses [122] comparing long-term outcomes in patients undergoing coronary stenting with various intravascular imaging modalities, IVUS guidance led to a significant reduction in cardiovascular death, recurrent MI, and stent thrombosis. Intravascular imaging can be useful for identifying the infarct-related coronary lesion when angiographic data are inconclusive and for optimizing PCI.

3.1.3. Pharmacoinvasive approach

The pharmacoinvasive strategy consists of prehospital thrombolytic therapy followed by coronary angiography with the intent to perform PCI of the infarct-related artery ("rescue" PCI—immediate PCI in the absence of evidence of myocardial reperfusion after thrombolysis or upon the development of life-threatening conditions; "routine early" PCI—within 2–24 hours after successful thrombolysis).

All cases of systemic thrombolytic therapy (successful and unsuccessful) should be considered solely as the initial component of the reperfusion strategy within a pharmacoinvasive approach—involving subsequent PCI (rescue, urgent, or delayed) within 24 hours of thrombolysis—rather than a complete substitute for primary PCI.

Dosing regimens for thrombolytic agents are provided in Appendix A3. Thrombolytic agents and their dosing regimens in STEMI.

If primary PCI cannot be performed within 120 minutes from the time of NSTE-ACS / STEMI diagnosis and no more than 12 hours have passed since symptom onset, it is recommended to initiate intravenous administration of thrombolytic agents (syn.: systemic thrombolytic therapy; group B01A - antithrombotic agents) as rapidly as possible (within 10 minutes of diagnosis) in the absence of contraindications to thrombolysis [74, 76].

ESC I A (LoE A, GoR 1)

Comment: Administration of the thrombolytic agent should be initiated within 10 minutes of diagnosis (the time allotted for thrombolysis organization is based on the median timeframe (9 minutes) recorded in the STREAM trial, which showed similar treatment outcomes between the primary PCI strategy and the pharmacoinvasive strategy) [49].

ECG criteria for thrombolytic therapy:

New-onset ST-segment elevation measured at the J point in at least two contiguous ECG leads of ≥ 0.1 mV in all leads other than leads V₂–V₃, where ST-segment elevation should be ≥ 0.2 mV in men aged 40 years or older, ≥ 0.25 mV in men younger than 40 years, or ≥ 0.15 mV in women (in the absence of left ventricular (LV) hypertrophy or left bundle branch block);
New (or presumed new) complete left bundle branch block;

Absolute contraindications to thrombolytic therapy:

— Prior intracranial hemorrhage or stroke of unknown etiology;

— Ischemic stroke within the preceding 6 months;

— Central nervous system damage or neoplasms, or central nervous system arteriovenous malformations;

— Recent major trauma / surgery / head trauma / gastrointestinal bleeding (within the preceding month);

— Known bleeding diathesis or bleeding disorders (excluding menstrual bleeding);

— Aortic dissection (suspected or confirmed);

— Non-compressible vascular punctures, liver biopsy, or lumbar puncture within the preceding 24 hours.

Relative contraindications to thrombolytic therapy:

— Transient ischemic attack within the preceding 6 months;

— Use of oral anticoagulants;

— Pregnancy and the 1st week postpartum;

— Refractory arterial hypertension: systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 110 mm Hg;

— Severe liver disease;

— Infective endocarditis;

— Traumatic or prolonged cardiopulmonary resuscitation;

— Active peptic ulcer disease.

Under conditions that justify systemic thrombolytic therapy as the initial reperfusion strategy (see above) in patients with STEMI, in the absence of contraindications, and when facilities are available (trained personnel, availability of a thrombolytic agent, external defibrillator, and cardiopulmonary resuscitation equipment) to reduce the risk of death, it is recommended to administer intravenous thrombolytic agents in the prehospital setting (syn.: prehospital thrombolysis) [123–125].

ESC IA (LoE A, GoR 1)

All patients with STEMI receiving systemic thrombolytic therapy (prehospital or in a hospital without PCI capabilities) are recommended to undergo immediate hospitalization or transfer to a medical facility with 24/7 PCI capabilities to reduce the risk of death [126–129].

ESC IA (LoE A, GoR 1)

Comment: In the period of 12–24 hours from the onset of STEMI symptoms, if PCI is not feasible, symptoms and signs of transmural ischemia (ST-segment elevation on the ECG) persist, and there are no contraindications to fibrinolytic therapy (FLT), FLT should be considered in selected patients (with a large threatened myocardial area and/or hemodynamic instability) to reduce the risk of death [14, 512, 513].

If systemic FLT is used in STEMI to reduce the risk of death, it is recommended to prefer fibrin-specific thrombolytics over non-fibrin-specific ones [130].

ESC I B (CQR B, LOR 2)

Comment: Evidence of the superiority of a fibrin-specific thrombolytic (alteplase**) over a non-fibrin-specific one (streptokinase) in terms of mortality has been demonstrated in only one study and was not confirmed in subsequent meta-analyses. The preference for fibrin-specific thrombolytics in this case is determined not so much by greater efficacy as by streptokinase's unfavorable tolerability profile (allergic reactions and the ability to cause arterial hypotension) and the unpredictable threat of neutralization of its effects by specific antibodies (in individual patients).

In STEMI patients older than 75 years, when choosing tenecteplase** for systemic FLT, it is recommended to use half of its standard dose [49, 131].

ESC IIaB (CQR A, LOR 2)

Comment: In patients with STEMI older than 75 years, if tenecteplase** is used to reduce the risk of bleeding, primarily intracranial bleeding, a half dose of this thrombolytic may be used [49, 131].

In case of unsuccessful systemic thrombolytic therapy in patients with STEMI (no reduction in ST-segment elevation on the ECG or a reduction of less than 50% from the baseline ST elevation 60–90 minutes after the start of intravenous thrombolytic infusion), urgent coronary angiography with the intent to perform "rescue" PCI is recommended to restore coronary artery patency, prevent myocardial infarction recurrence, and heart failure, and repeat systemic thrombolytic therapy is not recommended [132–136].

ESC IA (LoE A, GoR 1)

Comment: In studies comparing rescue PCI and conservative (without PCI) management of STEMI patients after failed FLT, in addition to a reduction in the risks of recurrent MI and heart failure, a statistically nonsignificant trend toward lower mortality was noted when rescue PCI was performed.

In STEMI patients, urgent CAG with the intention of performing rescue PCI is recommended prior to the time of evaluating the efficacy of systemic FLT (60–90 minutes from its initiation) if signs of hemodynamic (acute heart failure) or electrical (life-threatening arrhythmias) instability, progressive ischemia, or unremitting chest pain appear [132–136].

ESC IA (LoE A, GoR 1)

Following successful systemic FLT in STEMI patients, early CAG (2–24 hours after the end of FLT) with the intention of performing "early routine" PCI of the infarct-related artery is recommended (to reduce recurrent MI, the combined risk of recurrent MI and death, and to reduce the risk of recurrent myocardial ischemia) [127, 128].

ESC IA (LoE A, GoR 1)

Comment: Criteria for successful FLT are numerous, but in practice, the assessment of ST-segment shift in the most informative ECG lead is used (where the upward shift of the segment was greatest on the baseline ECG). Complete disappearance of ST-segment elevation 90 minutes after the start of FLT is desirable, but a 50% or greater reduction in ST-segment elevation from baseline is sufficient to consider FLT effective. In studies evaluating the effects of "facilitated" PCI, patients under such a strategy received not only FLT but also a glycoprotein IIb/IIIa (GP IIb/IIIa) receptor blocker. Currently, facilitated PCI is not recommended because in repeated comparisons with the "primary PCI strategy," it either showed no advantages or registered a higher frequency of adverse outcomes, including an increased risk of bleeding and death.

In case of recurrent myocardial ischemia or other signs of reocclusion (electrical or hemodynamic instability) after initially successful FLT in STEMI patients, to reduce the risk of death, it is recommended to abandon the strategy of "early routine" PCI (scheduled performance within 2–24 hours after the end of FLT) and perform urgent CAG to determine the feasibility and extent of PCI [137, 138].

ESC IC (LoE C, SoR 5)

If a patient with STEMI has failed to undergo CAG and PCI for any reason up to 24 hours after the end of FLT, it is recommended to perform CAG and determine the need for PCI in a later period of hospitalization (to reduce the risk of recurrent MI) [137].

ESC IC (LoE C, SoR 5)

Technical recommendations for performing PCI after FLT coincide with those for primary PCI (Section 3.1.2 Primary Percutaneous Coronary Intervention).

3.1.4. Renal protection during percutaneous coronary intervention

In STEMI patients with diabetes mellitus, it is recommended to take into account the higher risk of contrast-induced nephropathy, which must be considered when choosing the volume of radiocontrast agents and when deciding on the use of active prophylaxis (hydration), if the patient's condition permits [14, 139–142].

ESC IC (Level of Evidence B, Grade of Recommendation 2)

Comments: If the patient is receiving metformin** and/or a sodium-glucose cotransporter 2 (SGLT2) inhibitor, deterioration of renal filtration function can be expected after CAG/PCI. Therefore, it is recommended to discontinue metformin** prior to CAG/PCI, or to closely monitor renal filtration function in cases where the intervention cannot be delayed.

When performing CAG/PCI in STEMI patients with moderate or severe CKD, hydration with isotonic sodium chloride solution** and the use of a low- or iso-osmolar contrast agent (in minimal volume) are recommended for the prevention of acute kidney injury [139, 141–146].

ESC IIaB (CQR A, LOR 2)

Comments: In patients with moderate to severe CKD (eGFR 15–44 mL/min/1.73 m²), it is recommended to limit the volume of contrast medium administered (contrast volume to eGFR ratio < 3.7). If the expected volume of contrast medium during CA/PCI exceeds 100 mL, hydration with isotonic sodium chloride solution** is recommended – intravenous infusion at a rate of 1 mL/kg/h for 12 hours before the procedure (if feasible) and for at least 24 hours after its completion (0.5 mL/kg/h for patients with LVEF ≤ 35% or NYHA class > II CHF). Hydration protocols guided by central venous pressure (CVP) monitoring or IV furosemide** administration with fluid loss replacement using isotonic sodium chloride solution** may also be used.

In patients with severe CKD (eGFR 15–29 mL/min/1.73 m²), the feasibility of prophylactic hemofiltration 6 hours before PCI (if possible) with fluid replacement at a rate of 1000 mL/h without fluid loss and hydration for at least 24 hours after the procedure may be considered.

3.1.5. Spontaneous coronary artery dissection

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic coronary artery disease characterized by separation of the arterial intima with the formation of a subintimal hematoma and spontaneous (non-iatrogenic) obstruction of the arterial lumen. SCAD occurs in approximately 4% of all ACS cases, predominantly in women under 60 years of age. There are 3 angiographic types of SCAD: Type 1 – presence of multiple radiolucent lumens in the coronary artery; Type 2 – presence of a long, smooth lesion formed by a bulky intramural hematoma; Type 3 – focal stenosis that looks like an atherosclerotic plaque.

Clinical manifestations of SCAD do not differ from those of atherothrombosis; therefore, the initial strategy corresponds to standard guidelines for managing patients with ACS (including STEMI). The most accurate methods to confirm SCAD during CAG are intravascular imaging methods (IVUS and OCT).

In total coronary artery obstruction caused by SCAD, in the presence of patient hemodynamic instability, persistent signs of ischemia, and high risk of cardiovascular complications, the recommended revascularization strategy is to perform PCI using balloon dilation and/or implantation of a coronary stent*** to restore coronary blood flow [147–148].

ESC I C (LoE C, GoR 4)

Comments: Endovascular treatment strategies for patients with SCAD are currently not defined. The main technical aspects of endovascular treatment for patients with SCAD are reflected in the ESC consensus document [149], according to which IVUS or OCT should be considered to confirm SCAD (the presence of a false lumen and/or intramural hematoma) as the cause of coronary obstruction [149–151]. Intravascular imaging methods have high resolution and allow reliable identification of dissection, its type, the degree of lumen compromise, and the position of the intracoronary guidewire (in the true or false lumen).

பொருட்கIn patients with spontaneous coronary artery disease (CAD) dissection in the absence of CAD obstruction, low risk of recurrent events, and no signs of ischemia, optimal medical therapy is recommended until the spontaneous CAD dissection heals [151-154].

3.1.6. Coronary artery bypass grafting

CABG in patients with STEMI has limited application and is not considered among the primary approaches to myocardial reperfusion. It has not been studied in such patients in randomized trials. Nevertheless, in selected cases of STEMI at various times from disease onset, CABG may be discussed and should be performed.

To reduce the risk of death in patients with STEMI and ongoing or recurrent myocardial ischemia when PCI is not feasible or has failed, urgent CABG is recommended [14, 137, 138].

ESC IIaC (Level of Evidence C, Grade of Recommendation 5)

Comment: No dedicated randomized clinical trials comparing percutaneous and surgical revascularization in patients with ACS have been conducted. In STEMI, urgent CABG should be considered only if primary PCI is impossible, especially in the presence of ongoing ischemia or large areas of affected myocardium [155].

To reduce the risk of death and recurrent MI in patients with STEMI and PCI complications (failed stent deployment, stent fracture, recurrent acute stent thrombosis, dissection, or CAD perforation) that cannot be resolved by endovascular techniques, CABG is recommended [14, 137, 156].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

Comment: Except for clearly urgent cases (with ongoing myocardial ischemia, cardiogenic shock, mechanical complications of MI), the timing of CABG in STEMI is unclear. The timing is partly determined by the need to ensure hemorrhagic safety of the procedure by waiting 3–7 days after discontinuing a P2Y₁₂ platelet receptor inhibitor (ATC group: antiplatelet agents, excluding heparin) (ticagrelor** should be discontinued at least 3–5 days, clopidogrel** at least 5 days, and prasugrel at least 7 days before elective surgery). In selected stable patients with STEMI and multivessel CAD after successful primary PCI (with a high SYNTAX score, diabetes mellitus, low LVEF), CABG should be considered as an option for staged complete revascularization. When discussing CABG options in each specific case, one should consider the use of available mechanical circulatory support (before, during, and after surgery) and the choice of off-pump surgical techniques (e.g., off-pump CABG).

3.1.7. Reperfusion treatment in patients with cardiogenic shock and sudden cardiac arrest

In patients with STEMI and cardiogenic shock, prompt myocardial revascularization is recommended to improve prognosis [157].

ESC IIaB (LOCE B, LOE 2)

Comment: The choice between PCI and CABG in this clinical situation is determined by the coronary anatomy and the presence of mechanical complications of MI.

In patients with STEMI and cardiogenic shock, PCI with restoration of blood flow in the infarct-related CAD is recommended as the preferred reperfusion strategy, regardless of symptom onset time [49, 123-125, 158].

ESC IB (LoE B, LoR 2)

In patients with STEMI and cardiogenic shock, due to the potential increase in the risk of death and acute kidney injury / sharp progression of CKD, it is recommended to avoid immediate multivessel PCI, limiting the intervention to the infarct-related CAD [158].

ESC IIIB (LOC B, LE Level 2)

In patients with STEMI and cardiogenic shock when PCI is not feasible or has failed, urgent CABG is recommended to reduce the risk of death [157, 159, 160, 518, 519].

ESC IB (LoE B, LoR 2)

Comment: In the SHOCK trial, 302 patients with acute MI complicated by cardiogenic shock were randomized to emergency revascularization (PCI performed in 64% of cases, CABG in 36%) versus initial medical stabilization. About 60% of patients had anterior MI, and 85% had multivessel CAD. There was no difference in 30-day mortality (primary endpoint) between the emergency revascularization and initial medical stabilization groups, but at 6 months, mortality was lower in the emergency revascularization group. Based on these data, patients with acute MI complicated by cardiogenic shock are recommended to undergo immediate coronary angiography with the intent to perform PCI. For patients with coronary anatomy unsuitable for PCI, emergency CABG is recommended [157].

In patients with NSTE-ACS / STEMI and cardiogenic shock when primary PCI cannot be performed within 120 minutes of diagnosis and in the absence of mechanical complications of MI, systemic fibrinolytic therapy is recommended [76].

ESC IIaC (LoE C, GoR 5)

In patients with STEMI who have suffered cardiogenic shock and an index revascularization procedure, staged revascularization of non-infarct-related CAD is recommended in the presence of ongoing ischemia, hemodynamic instability, and taking into account comorbidities [137].

ESC IIaC (LoE C, GoR 5)

In patients with STEMI after successful resuscitation from sudden cardiac arrest, coronary angiography with the intent of primary PCI is recommended [126, 138].

ESC IB (LoE C, GoR 5)

In patients after successful resuscitation from sudden cardiac arrest, who are hemodynamically stable and have no diagnostically significant ST-segment deviation on the ECG for STEMI, routine immediate coronary angiography is not recommended [127-130, 132, 161].

ESC IIIA (CoE B, LOE 2)

Comments: The management strategy for patients with sudden cardiac arrest should be determined individually, taking into account the patient's condition, hemodynamic, and neurological characteristics. The lack of benefit of immediate coronary angiography in patients without ischemic ECG changes was demonstrated in the COACT trial [161]. At the same time, the presence of ST-segment elevation on the ECG is an indication for immediate coronary angiography and primary PCI.

3.1.8. Myocardial infarction with non-obstructive coronary arteries

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a "working" diagnosis established in patients meeting the criteria for MI according to the Fourth Universal Definition (Appendix A3. Diagnostic criteria for myocardial infarction) [5], when coronary angiography reveals no stenosis $\ge$ 50% in any major epicardial CAD.

The term "MINOCA" encompasses a heterogeneous group of pathologies, both coronary and non-coronary, including non-cardiac conditions. The main purpose of introducing this term is that a patient diagnosed with MINOCA requires further investigation to verify the definitive diagnosis and provide adequate treatment.

In patients with no obstructive CAD (stenoses of at least 50% on coronary angiography) in the presence of clinical and laboratory signs of MI, an extensive diagnostic workup is recommended to determine the cause of myocardial injury and verify the diagnosis [162, 163].

ESC IC (Level of Evidence C, Grade of Recommendation 4)

Comment: The diagnostic workup for patients with MINOCA includes echocardiography, coronary angiography with intravascular imaging methods (IVUS or OCT) to rule out mural thrombi, erosions, spontaneous CAD dissection, spasm provocation tests for epicardial CAD and microvascular dysfunction, as well as, if necessary, additional tests for the differential diagnosis of ACS (the list of tests is determined by clinical guidelines for the alternative diagnosis/diagnoses).

For etiological treatment, the management of patients with MINOCA is recommended in accordance with current guidelines regarding the specific diagnosed cause of MINOCA [162, 163].

ESC IB (LoE C, GoE 4)

In the absence of an obvious cause of MINOCA, cardiac magnetic resonance (CMR) imaging with contrast is recommended to clarify the cause of myocardial injury [164].

ESC IB (CGR B, LOR 3)

3.2. Medical treatment of the disease

3.2.1. Pain management

To relieve pain, provide sedation, and reduce sympathetic activity leading to tachycardia and increased blood pressure in patients with STEMI, intravenous administration of morphine** (group N02AA – natural opium alkaloids; syn.: narcotic analgesics) is recommended [165].

ESC IIaB (LoE C, GoR 4)

Comment: A distinctive feature of anginal pain in MI is a weak or absent response to nitroglycerin** (group C01DA – organic nitrates). Nevertheless, if the anginal pain does not subside within a few minutes after cessation of the provoking factor (physical exertion) or if it occurs at rest, the patient should take sublingual nitroglycerin** tablets or spray at a dose of 0.4–0.5 mg. If symptoms do not resolve after 5 minutes and the drug is well tolerated, it can be repeated. If pain or chest discomfort persists for 5 minutes after the repeat dose of nitroglycerin**, emergency medical services must be called immediately. If 2–3 doses of nitroglycerin** do not reduce the intensity of the attack, further administration is pointless. Due to the risk of hypotension, blood pressure should be continuously monitored.

In addition to analgesia, morphine** helps reduce fear and agitation, decreases sympathetic activity, increases vagal tone, reduces the work of breathing, and causes dilation of peripheral arteries and veins (the latter is especially important in pulmonary edema). The dose required for adequate analgesia depends on individual sensitivity, age, and body size. Before use, 10 mg of morphine** should be diluted in at least 10 ml of 0.9% sodium chloride** solution (group B05BB – solutions affecting the electrolyte balance). Initially, 2–4 mg of the drug substance should be administered IV slowly. If necessary, administration is repeated every 5–15 minutes in doses of 2–4 mg until pain relief is achieved or side effects occur that preclude increasing the dose.

The administration of morphine** leads to a delayed and attenuated primary effect of antiplatelet agents (clopidogrel**, ticagrelor**, prasugrel), which may affect treatment outcomes in some patients [166-168].

When using morphine**, the following complications are possible:

severe arterial hypotension; reversed by a horizontal position combined with leg elevation (if there is no pulmonary edema). If this is insufficient, 0.9% sodium chloride** solution is administered IV drip. In rare cases—adreno- and dopamine receptor agonists (group C01CA – adrenergic and dopaminergic agents);
severe bradycardia combined with arterial hypotension; reversed with atropine** (IV 0.5–1.0 mg);
nausea, vomiting; reversed with phenothiazine derivatives, specifically metoclopramide** (IV single dose 10 mg);

marked respiratory depression; reversed with naloxone** (IV 0.1–0.2 mg, repeated every 15 min if necessary), which also reduces the analgesic effect of the drug.

Opiates can weaken intestinal peristalsis and lead to constipation. Drugs of this group reduce bladder tone and cause urinary retention, especially in men with prostatic hyperplasia.

In the presence of signs of severe anxiety and/or agitation in patients with STEMI, it is recommended to administer tranquilizers (group N05BA – benzodiazepine derivatives) to relieve them [14, 169-170].

ESC IIaC (LoE C, GoR 5)

Comment: To reduce fear, it is usually sufficient to create a calm environment and administer a narcotic analgesic. In cases of severe agitation, tranquilizers may be required (e.g., diazepam** IV 5–10 mg, starting dose for the elderly is 2.5 mg; group N05BA – benzodiazepine derivatives). An appropriate behavioral style of the staff, explanation of the diagnosis, prognosis, and treatment plan are of great importance for the patient's emotional comfort. In patients with persistent anxiety and behavioral disturbances, as well as withdrawal symptoms in nicotine dependence, tranquilizers can also be prescribed. For agitation and delirium, IV administration of haloperidol** is quite effective and safe.

3.2.2. Correction of hypoxemia

In patients with STEMI, in the presence of hypoxemia (blood hemoglobin oxygen saturation level (SpO₂) < 90% or arterial blood partial pressure of oxygen (PaO₂) < 60 mm Hg), it is recommended to administer oxygen via inhalation (oxygen therapy) to correct it [14, 171].

ESC IC (RR S, ELD 5)

Comment: Humidified oxygen is delivered via nasal catheters at a rate of 2–8 l/min. Blood oxygen saturation is monitored by measuring SpO₂non-invasively or by assessing blood gas parameters (primarily PaO₂) using laboratory tests.

Due to the lack of positive effects on the disease course, oxygen administration via inhalation (oxygen therapy) is not recommended for patients with STEMI with a blood oxygen saturation level (SpO₂)≥ 90% [14, 171].

ESC IIIB (LoE A, GoR 2)

Comment: Oxygen inhalation (oxygen therapy) is not only of no benefit to patients with uncomplicated STEMI, but may be harmful, presumably due to increased myocardial injury [172].

3.2.3. Antithrombotic therapy

Dosing regimens for antithrombotic agents in STEMI are provided in Appendix A3. Medical treatment of STEMI in impaired renal filtration function is provided in Appendix A3. Doses of antithrombotic drugs in impaired renal function.

3.2.3.1. Antithrombotic support for thrombolytic therapy

Antiplatelet agents in thrombolytic therapy

To reduce the risk of death, vascular death, reinfarction, and ischemic stroke, all patients with STEMI (regardless of the treatment strategy) with no contraindications are recommended to take acetylsalicylic acid** (ASA**) in an initial loading dose, followed by a maintenance dose indefinitely [14, 173, 174].

ESC IA (LoE A, GoR 1)

Comments: An initial (loading) dose of ASA** (group B01AC – platelet aggregation inhibitors excluding heparin) of 150–300 mg (chew and swallow the tablet) as soon as possible after the diagnosis of ACSSTE / STEMI is established; a continuous maintenance dose of ASA** of 75–100 mg orally once daily starting from the second day of patient management [14, 174]. The use of ASA** at the pre-hospital stage lacks evidence of efficacy and safety (compared to the studied use in the hospital), but patients receiving pre-hospital thrombolysis are an exception (ASA** should be administered before or during the administration of the thrombolytic).

To reduce the risk of death, recurrent MI, the combined risk of ischemic events (cardiovascular death, MI, stroke, refractory ischemia requiring revascularization) in patients with STEMI when choosing a pharmacoinvasive strategy, in addition to ASA**, as a P2Y₁₂ platelet receptor inhibitor in the absence of contraindications, clopidogrel** is recommended – before or during thrombolytic therapy [14, 178, 179].

ESC IB (CQR A, LOR 2)

Comment: In patients with pre-hospital thrombolysis, the use of clopidogrel** (group B01AC – platelet aggregation inhibitors, excluding heparin) is justified already at the pre-hospital stage (clopidogrel** in a loading dose of 300 mg orally should be administered before or during the administration of the thrombolytic). The maintenance dose of clopidogrel** is 75 mg once daily orally for 12 months. In patients older than 75 years, treatment with clopidogrel should be carried out without a loading dose.

Clopidogrel** after its use during thrombolytic therapy can be replaced fairly early (within 24 hours from the start of thrombolytic therapy) with ticagrelor** (group B01AC – platelet aggregation inhibitors, excluding heparin), both within a pharmacoinvasive approach and in patients who received only a thrombolytic (without subsequent PCI). The safety of such "early" switching from clopidogrel** to ticagrelor** was demonstrated in the TREAT trial [180], and the greater efficacy of ticagrelor** (compared to clopidogrel**) in reducing the risk of ischemic events (combined risk of cardiovascular death, MI, and ischemic stroke) in this clinical situation is proposed to be extrapolated from the results of the PLATO trial [181], which did not include STEMI patients who received thrombolytic therapy.

The possibility of an early switch from clopidogrel** to ticagrelor** in STEMI patients who received a thrombolytic does not apply to individuals older than 75 years. Evidence for the feasibility and safety of an early switch from clopidogrel** to prasugrel (group B01AC – platelet aggregation inhibitors, excluding heparin) in STEMI patients who received thrombolytic therapy, in the form of randomized controlled trial results, does not exist.

Premature discontinuation of dual antiplatelet therapy – cessation of both antiplatelet agents – increases the rate of coronary complications. A frequent reason for the premature discontinuation of one or both components of dual antiplatelet therapy is bleeding and the need for surgery. If it is necessary to discontinue a P2Y₁₂ platelet receptor inhibitor due to surgery, it is highly desirable to perform this procedure in a multidisciplinary hospital with the capability of performing PCI in the event of perioperative stent thrombosis and MI.

If emergency non-cardiac surgery or major bleeding occurs, treatment with a P2Y₁₂-receptor inhibitor should be discontinued and resumed at the earliest opportunity after the causes of bleeding are eliminated.

Ticagrelor** should be discontinued at least 3 days, clopidogrel** at least 5 days, and prasugrel at least 7 days before elective surgery. Whenever possible, ASA** should be continued, as discontinuing both drugs further increases the risk of coronary thrombosis. If the specified timeframes cannot be met, the decision on surgical treatment should be made by a multidisciplinary medical team, which must assess the risks of bleeding and discontinuation of dual antiplatelet therapy, as well as take into account the type of surgery, the risk of myocardial ischemia recurrence, the extent of coronary artery disease, the time elapsed from STEMI onset and PCI, and the characteristics of implanted stents. In surgeries with a low bleeding risk, dual antiplatelet therapy should not be interrupted prematurely.

In STEMI patients undergoing systemic thrombolytic therapy (TLT) as a reperfusion strategy, ticagrelor** and prasugrel (both before and during TLT) are not recommended in addition to ASA** due to the lack of evidence of safety for this approach [14, 180-184].

ESC IIIC (CGR C, LOR 5)

In STEMI patients with a high risk of subsequent ischemic events and a low bleeding risk, with no history of stroke or TIA, and regardless of the presence/absence and type of prior reperfusion therapy (i.e., including post-TLT), after discontinuation of parenteral anticoagulant infusion, rivaroxaban** orally at a dose of 2.5 mg twice daily for 12 months (in selected cases up to 24 months) is recommended in addition to the combination of ASA** and clopidogrel** to reduce the risk of ischemic events [185].

ESC IIbB (Level of Evidence A, Grade of Recommendation 1)

Comments: Administration of rivaroxaban** at 2.5 mg twice daily in addition to the combination of ASA** and clopidogrel** should be initiated within the first week of STEMI treatment onset, following myocardial revascularization procedures (if indicated) and cessation of parenteral anticoagulants [185].

The addition of rivaroxaban** at 2.5 mg twice daily has not been studied in combination with dual antiplatelet therapy containing prasugrel or ticagrelor**. This approach cannot be used in patients requiring higher doses of oral anticoagulants (particularly in the presence of atrial fibrillation (AF) with an elevated stroke risk).

In STEMI patients undergoing systemic thrombolytic therapy (TLT) as a reperfusion strategy, glycoprotein (GP) IIb/IIIa receptor blockers (both before and during TLT) are not recommended in addition to ASA** due to the lack of evidence of efficacy and indications of an increased bleeding risk [186, 187].

ESC IIIB (LOC B, LE Level 2)

In STEMI patients with a high risk of gastrointestinal bleeding during dual antiplatelet therapy, regardless of prior reperfusion treatment, proton pump inhibitors are recommended for gastric mucosal protection and reduction of gastrointestinal bleeding risk [188, 189].

ESC IA (LoE A, GoR 2)

Comments: The risk of gastrointestinal bleeding is increased in patients with a history of peptic ulcer disease or gastrointestinal bleeding, chronic use of nonsteroidal anti-inflammatory drugs or corticosteroids, as well as in the presence of at least 2 of the following features – age ≥ 65 years, dyspepsia, gastroesophageal reflux, Helicobacter pylori infection, chronic alcohol consumption).

A potential attenuation of the antiplatelet effect of clopidogrel** (based on laboratory platelet reactivity assays) has been reported when combined with omeprazole** or esomeprazole**, but not with pantoprazole or rabeprazole. There is no evidence that these drug interactions adversely affect clinical treatment outcomes.

Parenteral anticoagulants during TLT

Parenteral anticoagulants (group B01A - antithrombotic agents) are recommended for all STEMI patients regardless of treatment strategy (including as an adjunct to systemic TLT) initiated as early as possible after the diagnosis of NSTE-ACS / STEMI [14, 190-195].

ESC I A (LoE A, GoR 1)

Comment: During TLT, the duration of parenteral anticoagulant administration ranges from 2 to 8 days, unless there are other indications for its extension [104, 358].

As a parenteral anticoagulant of first choice (compared to unfractionated heparin (UFH; syn.: heparin sodium**)) to support systemic TLT in STEMI patients, enoxaparin sodium** is recommended [196, 197].

ESC IA (LoE A, LoR 2)

Comment: The repeatedly demonstrated superiority of enoxaparin sodium** (group B01AB – heparin group) over heparin sodium** (group B01AB – heparin group) applies primarily to patients receiving fibrin-specific thrombolytics [196-200]. However, evidence supporting its use is also available in patients treated with streptokinase [201, 202]. Importantly, enoxaparin sodium** did not show an advantage in terms of hemorrhagic safety in the aforementioned comparisons.

As a parenteral anticoagulant to support systemic TLT in STEMI patients, the factor Xa inhibitor fondaparinux sodium is recommended to reduce the composite risk (death and recurrent MI) [203].

ESC IIaB (LoE B, GoR 2)

Comment: The superiority of fondaparinux sodium over UFH**/placebo in the complex OASIS-6 trial [203] was demonstrated mainly in the subgroup of patients receiving streptokinase, where fondaparinux was compared with placebo in the majority of cases. However, in patients receiving other thrombolytics, including fibrin-specific ones, it was at least as good as UFH**. It should be remembered that fondaparinux is the drug of choice in mild-to-moderate thrombocytopenia or when there is a threat of heparin-induced thrombocytopenia.

As a parenteral anticoagulant to support systemic TLT in STEMI patients, heparin sodium** is recommended [196-200].

ESC IIbB (LoE C, SoE 5)

Comment: Heparin sodium** is administered as an intravenous bolus followed by a continuous intravenous infusion with monitoring of activated partial thromboplastin time (aPTT) and adjustment of the infusion rate to maintain the aPTT within 1.5-2.0 times the upper limit of normal.

Among the proven effects of anticoagulation with heparin sodium** is better patency of the infarct-related artery several days after thrombolytic administration. Intravenously administered UFH** (as an adjunct to TLT) lacks evidence of efficacy in reducing the risk of major ischemic events or death compared to either placebo or other anticoagulants. Nevertheless, like ASA**, it has been a mandatory component of TLT adjunct therapy for decades in patients receiving fibrin-specific thrombolytics (tissue plasminogen activator derivatives, mainly al teplase**). The priority positions of UFH**, lost in direct comparisons with enoxaparin** [196-202], remain unchanged when choosing an anticoagulant as an adjunct to TLT in patients with severe renal excretion impairment and in patients with very high or very low body weight. It is implied that in each of these cases, the aPTT-titrated infusion rate of UFH** is intended to make treatment in such patients more effective and safe.

3.2.3.2. Antithrombotic therapy in other treatment strategies

"Other treatment strategies" in this section refer to the performance of PCI, CABG, and the absence of any reperfusion therapy.

Antiplatelet agents in other treatment strategies for patients without indications for long-term oral anticoagulation

To reduce the risk of death, vascular death, recurrent MI, and ischemic stroke, all STEMI patients without contraindications (regardless of the treatment strategy) are recommended to receive ASA** in an initial loading dose followed by a maintenance dose indefinitely [14, 173, 174].

ESC IA (LoE A, GoR 1)

Comments: An initial (loading) dose of 150- 300 mg (tablet chewed and swallowed) is recommended as soon as possible after the diagnosis of NSTE-ACS / STEMI; a continuous maintenance dose of ASA** of 75-100 mg orally once daily starting from the second day of patient management [14, 174].

The use of ASA** in the prehospital setting lacks evidence of efficacy and safety (except for patients undergoing prehospital thrombolysis). The justification for using ASA** in patients undergoing primary PCI stems from the fact that the efficacy of PCI in clinical trials was demonstrated in STEMI patients who received ASA** as mandatory background therapy.

All patients with STEMI (regardless of the treatment strategy, except for planned CABG) without a high risk of bleeding, in addition to ASA**, are recommended P2Y₁₂ platelet receptor inhibitors (group B01AC - platelet aggregation inhibitors, excluding heparin) at an initial loading dose followed by a maintenance dose for 12 months to reduce the cumulative risk of death, MI, and ischemic stroke [14, 175-178, 182-184].

ESC IA (LoE A, GoR 2)

Comments: The choice of a P2Y₁₂ platelet receptor inhibitor to accompany reperfusion therapy is determined by the reperfusion strategy, drug availability, and individual characteristics that limit the safety of their use in certain categories of STEMI patients.

The use of a P2Y₁₂ platelet receptor inhibitor should be avoided in STEMI with a high probability of urgent CABG (known coronary artery disease unsuitable for PCI; CABG in addition to surgery for mechanical complications of STEMI — repair of ventricular septal defect or free wall rupture, mitral valve replacement).

As with ASA**, the justification for prehospital administration of a P2Y₁₂ platelet receptor inhibitor lacks evidence of efficacy and safety regarding ischemic events derived from randomized controlled trials. An additional argument against prehospital use of these agents is the increased risk of death in the first 24 hours of treatment in patients who received ticagrelor** as preparation for primary PCI in the ATLANTIC trial [204].

Hypothetically, prehospital administration of a P2Y₁₂ inhibitor to STEMI patients can be considered if two conditions are met: 1) there is no doubt about the diagnosis (characteristic clinical presentation and typical ECG changes); 2) there is coordination between the prehospital team and the invasive center, and a high probability of emergency PCI. At the same time, failure to administer a P2Y₂inhibitor before PCI cannot be a reason for delaying the intervention. There are no grounds to include prehospital administration of P2Y₁₂ inhibitors in the list of mandatory procedures. Accordingly, failure to administer P2Y₁₂inhibitors cannot be considered a tactical error. If there are doubts about the diagnosis of STEMI and treatment tactics, the administration of P2Y₁₂ inhibitors is justified to be postponed until coronary anatomy is assessed.

The risks and tactics of early discontinuation of dual antiplatelet therapy are described in the section "Antiplatelet Agents and Thrombolytic Therapy" (supplement for patients who underwent PCI: prasugrel should be discontinued at least 7 days before elective surgery). If interruption of dual antiplatelet therapy is absolutely necessary in a patient with coronary stent(s), it should be borne in mind that there is no alternative, safer option for stent thrombosis prophylaxis.

The recommendation on the need for gastric mucosa protection and reduction of the risk of gastrointestinal bleeding during dual antiplatelet therapy does not depend on prior reperfusion treatment and is outlined in the section "Antiplatelet Agents and Thrombolytic Therapy".

If dual antiplatelet therapy (ASA** combined with a P2Y₁₂ platelet receptor inhibitor) in a STEMI patient was delayed or interrupted due to CABG surgery, it is recommended to initiate or resume it after CABG surgery for 12 months to reduce the risk of ischemic events [14].

ESC IC (LoE C, SoR 5)

Prasugrel (loading dose 60 mg, daily maintenance dose 10 mg orally) in addition to ASA** for 12 months is recommended to reduce the risk of ischemic events during coronary stenting in STEMI patients who have not received other P2Y₁₂ platelet receptor blockers, provided there are no contraindications to it (history of intracranial hemorrhage, history of ischemic stroke/transient ischemic attack, active bleeding) [176].

ESC IB (LoE B, LoR 2)

Comments: The safety of switching to prasugrel in patients who have already received clopidogrel** has not been sufficiently studied. Prasugrel treatment does not preclude the use of a glycoprotein IIb/IIIa receptor blocker during PCI. In patients aged ≥ 75 years or with a body weight < 60 kg, the maintenance daily dose of prasugrel must be reduced to 5 mg.

In STEMI, prasugrel is not recommended for use prior to diagnostic coronary angiography and the decision to perform PCI due to an increased risk of bleeding [183, 184].

ESC IIIB (CGR B, LOR 2)

Ticagrelor** (loading dose 180 mg, maintenance dose 90 mg twice daily orally) to reduce the risk of ischemic events is recommended in addition to ASA** for 12 months in STEMI patients both with invasive reperfusion and in the absence of any reperfusion therapy, and regardless of prior clopidogrel** use, provided there are no contraindications to it (history of intracranial hemorrhage, active bleeding) [175].

ESC I B (LE A, LoE 2)

Comment: Switching to ticagrelor**, starting with a loading dose, is possible in patients who have already received clopidogrel**, including at a loading dose. Ticagrelor** treatment does not preclude the use of glycoprotein IIb/IIIa receptor blockers during PCI.

When performing primary PCI in STEMI patients, in addition to ASA**, it is recommended to prefer prasugrel over ticagrelor** [183, 184].

ESC IIaB (LE B, LoE 2)

In the case of invasive reperfusion or absence of any reperfusion therapy in STEMI patients who cannot receive ticagrelor** or prasugrel due to contraindications, intolerance, or unavailability, to reduce the risk of ischemic events in addition to ASA**, it is recommended clopidogrel** (loading dose 600 or 300 mg, maintenance dose 75 mg once daily orally) for 12 months [177, 205].

ESC I B (LE A, LoE 2)

Comments: If PCI is performed, a clopidogrel** loading dose of 600 mg is recommended; in other cases, a loading dose of 300 mg.

In STEMI patients with a high risk of subsequent ischemic events and a low risk of bleeding, with no history of stroke or transient ischemic attack, and regardless of the presence/absence and type of prior reperfusion therapy (i.e., including after invasive reperfusion or in the absence of any reperfusion therapy), after discontinuing parenteral anticoagulation, in addition to the combination of ASA** and clopidogrel** to reduce the risk of ischemic events, it is recommended rivaroxaban** at a dose of 2.5 mg twice daily for 12 months (in selected cases – up to 24 months) [185].

ESC IIbB (Level of Evidence A, Grade of Recommendation 1)

In invasive reperfusion or in the absence of any reperfusion therapy in elderly STEMI patients, especially in the presence of a high risk of bleeding, in addition to ASA**, it is recommended to consider clopidogrel** (rather than ticagrelor** or prasugrel) to improve treatment adherence and reduce the risk of bleeding [14, 206, 207].

ESC IIbB (LE A, LoE 2)

Comments: In clinical trials, elderly patients were defined as those older than 70–80 years. When making a decision, it is also recommended to take into account the presence and severity of frailty and comorbidities.

In STEMI patients, glycoprotein IIb/IIIa receptor inhibitors (abciximab, tirofiban, eptifibatide, monoclonal antibody fragments FRaMon F[ab`]2) are recommended only as a bailout therapy in case of thrombotic complications or the slow flow / no-reflow phenomenon during PCI [14, 208].

ESC IIaC (LoE C, GoR 5)

Comments: Glycoprotein IIb/IIIa platelet inhibitors were studied mainly before the widespread use of P2Y₁₂ platelet receptor blockers [208]. In addition to complications during PCI, the administration of a GP IIb/IIIa inhibitor may be considered in high-risk PCI in patients who have not received a P2Y₁₂-receptor blocker and have massive intracoronary thrombosis.

Due to the high risk of bleeding, which outweighs the potential benefit, in STEMI patients it is not recommended to use ASA** if the platelet count is less than 10×10⁹/L, clopidogrel** – less than 30×10⁹/L, ticagrelor** or prasugrel – less than 50×10⁹/L [14, 209].

ESC III C (LE C, LoE 5)

Parenteral anticoagulants in other treatment strategies in patients without indications for long-term oral anticoagulation

To reduce the risk of ischemic events, it is recommended to initiate parenteral anticoagulation after confirming the diagnosis of STEMI in patients without contraindications. When choosing a drug, the risk of potential ischemic complications and bleeding, as well as the efficacy and safety profile of the specific anticoagulant, should be considered [190].

ESC IA (LoE A, GoR 1)

Comments: Anticoagulants must be used in combination with antiplatelet agents.

In patients already receiving vitamin K antagonists prior to STEMI development, parenteral anticoagulants (including during PCI) should not be used, provided that INR values of ≥ 2.0 (≥ 2.5 during PCI) are maintained. In patients receiving direct oral anticoagulants, an intravenous bolus of UFH** is recommended during PCI, regardless of the time elapsed since the last dose of the direct oral anticoagulant. A similar approach is recommended in patients receiving vitamin K antagonists with INR values < 2.5.

Due to the potential increase in bleeding risk, continuation of anticoagulation in STEMI patients after successful PCI is generally not recommended, unless there are other indications for therapeutic (atrial fibrillation, left ventricular thrombus, venous thrombosis, or PE) or prophylactic (severe heart failure, patient immobility) anticoagulation [14].

ESC IIIC (LoE C, GoR 5)

Note: If PCI is not performed in the early stages of STEMI, parenteral anticoagulant therapy should be continued for up to 8 days (with earlier discontinuation if PCI is performed or the patient is discharged during this period); the minimum duration of parenteral anticoagulation following thrombolytic therapy in non-invasive STEMI management is 24–48 hours.

During PCI in a patient with STEMI, an intravenous bolus of #heparin sodium** at a dose of 70–100 IU/kg is recommended [14].

ESC IC (Level of Evidence C, Grade of Recommendation 5)

Notes: Intravenous infusion of UFH** should be administered at a dose that maintains aPTT at 1.5–2.5 times the laboratory control value. When using UFH** during PCI, an intravenous bolus of 70–100 IU/kg is recommended; the need for repeat boluses is determined by the activated clotting time (ACT). Similar approaches are recommended for urgent PCI in patients receiving direct oral anticoagulants. If PCI is performed against the background of an ongoing intravenous UFH** infusion, additional intravenous boluses of UFH** under ACT monitoring should be considered during the procedure.

During PCI in patients with STEMI, as an alternative to unfractionated heparin** to reduce the risk of ischemic events, enoxaparin sodium** is recommended [193].

ESC IIaB (CQR A, LOR 2)

Notes: Enoxaparin sodium** is not recommended when the estimated glomerular filtration rate (eGFR) is below 15 mL/min/1.73 m². Switching from UFH** to enoxaparin sodium** and from enoxaparin sodium** to UFH** is not recommended due to an increased risk of bleeding.

If a STEMI patient received enoxaparin sodium** prior to PCI, it should be continued during the procedure; furthermore, if more than 8 hours have elapsed between the subcutaneous injection and balloon inflation in the coronary artery, an additional intravenous bolus of 0.3 mg/kg of the drug is recommended [14, 193, 526].

ESC IIaB (Level of Evidence B, Grade of Recommendation 3)

In STEMI patients, the use of bivalirudin is recommended to be considered as an alternative to UFH** for antithrombotic support during PCI [210-214].

ESC IIaA (LeveL of Evidence B, Grade of Recommendation 1)

Notes: Bivalirudin is the drug of choice in patients with heparin-induced thrombocytopenia. Bivalirudin infusion should be initiated simultaneously with PCI and continued for up to 4 hours after its completion.

The recommendation to use bivalirudin as an alternative to the combination of UFH** with a platelet GP IIb/IIIa receptor blocker during PCI has lost its relevance because, under the widespread use of dual antiplatelet therapy, the use of GP IIb/IIIa receptor blockers is mostly limited to cases of thrombotic complications during PCI.

In STEMI patients undergoing primary PCI, the administration of fondaparinux sodium is not recommended [203].

ESC IIIB (LOC B, LE Level 2)

Notes: For a patient who has nevertheless received fondaparinux sodium prior to PCI, UFH** should be administered intravenously during PCI – an initial bolus at a dose of 85 IU/kg; the need for repeat boluses is determined by the blood ACT value. Fondaparinux sodium is contraindicated in severe renal filtration impairment (eGFR below 20 mL/min/1.73 m²).

Antithrombotic therapy in other treatment strategies for patients with indications for long-term oral anticoagulation

In STEMI patients with indications for long-term anticoagulation who were not taking them for any reason at the time of STEMI onset, it is recommended to initiate antithrombotic treatment with triple antithrombotic therapy (a combination of ASA**, a platelet P2Y₁₂ receptor blocker, and a parenteral anticoagulant) followed by switching the parenteral anticoagulant to an oral one (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban, or a vitamin K antagonist) [14, 527-534].

ESC IA (LoE A, GoR 1)

Notes: Indications for long-term anticoagulation: atrial fibrillation / atrial flutter; mechanical heart valve prosthesis left ventricular thrombus, deep vein thrombosis (DVT), and/or prior PE.

In patients already receiving (prior to STEMI development) vitamin K antagonists, parenteral anticoagulants (including during PCI) should not be used, provided that INR values of ≥ 2.0 (≥ 2.5 during PCI) are maintained.

In patients receiving direct oral anticoagulants, an intravenous bolus of UFH** is recommended during PCI regardless of the time elapsed since the last dose of the direct oral anticoagulant; a similar approach is recommended in patients receiving vitamin K antagonists with INR values < 2.5.

In the absence of reperfusion therapy in patients receiving direct oral anticoagulants, the use of parenteral anticoagulants is recommended at the onset of STEMI management.

In STEMI patients with indications for long-term anticoagulation who have undergone coronary stenting or have not received reperfusion therapy, the duration of triple antithrombotic therapy (combination of an anticoagulant with ASA** and clopidogrel**) should be limited to a few days (1–7 days). After 1–7 days, upon discontinuation of ASA**, it is recommended to switch to dual antithrombotic therapy (an oral anticoagulant combined with clopidogrel**) [14, 215-220].

ESC IA (LoE C, GoR 5)

Notes: In selected patients at very high risk of coronary thrombosis and low bleeding risk, the use of ticagrelor** instead of clopidogrel** for 6 months may be considered.

In STEMI patients with indications for long-term anticoagulation (particularly with atrial fibrillation) who have undergone coronary stenting and are at high risk of coronary complications (including specific coronary anatomy and/or invasive procedure features), in whom the expected benefit outweighs the bleeding risk, it is recommended to consider extending triple antithrombotic therapy (combination of an oral anticoagulant with ASA** and clopidogrel**) up to 1 month, followed by discontinuation of ASA** and switching to dual antithrombotic therapy (combination of an oral anticoagulant with clopidogrel**) to reduce the risk of stent thrombosis [14, 218].

ESC IIaC (LoE C, GoR 4)

Notes: In selected patients at very high risk of coronary thrombosis and low bleeding risk, the use of ticagrelor** instead of clopidogrel** for 6 months may be considered.

Dual antithrombotic therapy (an oral anticoagulant combined with clopidogrel**, less commonly with ASA**) in STEMI patients with indications for long-term anticoagulation is recommended up to 12 months, after which clopidogrel** (or ASA**) should be discontinued and monotherapy with an oral anticoagulant continued at the dose necessary for the prevention and/or treatment of thrombotic and/or thromboembolic complications [215-220].

ESC IA (LoE A, GoR 2)

Notes: In patients at high risk of bleeding, switching to oral anticoagulant monotherapy is possible 6 months after PCI. A similar approach can be considered for a broader population of STEMI patients requiring long-term oral anticoagulation.

In selected patients with a low bleeding risk and a persistently high risk of coronary complications, extension of dual antithrombotic therapy (combination of an oral anticoagulant with clopidogrel** or ASA**) for more than 12 months may be considered.

In STEMI patients with non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents, direct oral anticoagulants are preferred over vitamin K antagonists, provided there are no contraindications [215–220].

ESC IB (LoE A, LoR 1)

Note: Data on the comparative efficacy of direct oral anticoagulants and warfarin** in myocardial infarction patients are limited to subgroup analyses in randomized controlled trials.

In STEMI patients with non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents, apixaban** at a dose of 5 mg twice daily or 2.5 mg twice daily is recommended to prevent thromboembolic complications, provided there are no contraindications [218].

ESC IIaB (LoE B, GoR 2)

Comments: According to available data, apixaban** is safer than warfarin** as part of dual and triple antithrombotic therapy, with a similar rate of coronary events compared to warfarin**. Apixaban** has been studied both in patients with STEMI who underwent percutaneous coronary intervention (PCI) and in those receiving non-invasive STEMI treatment.

The standard dose of apixaban** in this clinical situation is 5 mg twice daily. If at least 2 of the following factors are present – age ≥ 80 years, body weight ≤ 60 kg, serum creatinine ≥ 133 µmol/L – a dose of 2.5 mg twice daily is used).

In patients with STEMI and non-valvular atrial fibrillation who require a combination of anticoagulants and antiplatelet agents to prevent thromboembolic complications, dabigatran etexilate** at a dose of 150 mg twice daily (or 110 mg twice daily if contraindicated) is recommended [215].

ESC IIaB (LoE B, GoR 2)

Comments: Dabigatran etexilate** at doses of 110 or 150 mg twice daily as part of dual antithrombotic therapy (combined predominantly with clopidogrel**) in patients who underwent coronary stenting is safer than triple antithrombotic therapy (a combination of warfarin**, predominantly clopidogrel**, and ASA**). At the same time, a trend toward a higher rate of coronary events was noted with the 110 mg twice daily dose of dabigatran etexilate**. Therefore, as part of dual antithrombotic therapy (in combination with clopidogrel**) after coronary stenting, it is recommended to use dabigatran etexilate** at a dose of 150 mg twice daily; a dose of 110 mg twice daily as part of dual antithrombotic therapy may be preferred in patients with a predominant bleeding risk. As part of triple antithrombotic therapy for non-valvular atrial fibrillation, a dose of 110 mg twice daily is preferred.

In patients with STEMI and non-valvular atrial fibrillation who require a combination of anticoagulants and antiplatelet agents to prevent thromboembolic complications in the absence of contraindications, rivaroxaban** at a dose of 20 mg once daily (15 mg once daily if creatinine clearance is 30–49 ml/min) is recommended, and in patients with a predominant bleeding risk, 15 mg once daily (10 mg once daily if creatinine clearance is 30–49 ml/min) [14, 217, 520, 537].

ESC IB (LoE B, LoR 2)

Comments: Rivaroxaban** at a dose of 15 mg once daily (10 mg once daily if creatinine clearance is 30–49 ml/min) in combination predominantly with clopidogrel** in patients who underwent coronary stenting is safer than triple antithrombotic therapy (a combination of warfarin**, predominantly clopidogrel**, and ASA**). If the risk of cardioembolic and coronary events outweighs the bleeding hazard, standard doses of rivaroxaban** recommended for patients with non-valvular atrial fibrillation (20 mg once daily, or 15 mg once daily if creatinine clearance is 30–49 ml/min) are recommended.

In patients with STEMI and non-valvular atrial fibrillation receiving vitamin K antagonists in combination with antiplatelet drugs, it is recommended to maintain the INR within the range of 2.0–2.5 to ensure bleeding safety, with the time in the therapeutic range (TTR) being at least 70% [14].

ESC IIaB (LOCE C, LOE 5)

Comments: Target INR values for other indications for vitamin K antagonists may be higher (e.g., in patients with mechanical heart valve prostheses or following thromboembolic events occurring despite the specified INR values).

In patients with suspected STEMI receiving an oral anticoagulant, to reduce the risk of bleeding, it is not recommended to use platelet P2Y₁₂ receptor blockers until coronary angiography results are obtained and a decision on PCI is made, and the advisability of using platelet glycoprotein IIb/IIIa receptor inhibitors should be considered only in obvious thrombotic complications of PCI [14].

ESC IIIC (CGR C, LOR 5)

To protect the gastric mucosa and reduce the risk of gastrointestinal bleeding during triple antithrombotic therapy (combination of an oral anticoagulant with a platelet P2Y₁₂ receptor blocker and ASA**) or dual antithrombotic therapy (combination of an oral anticoagulant with a platelet P2Y₁₂ receptor blocker or ASA**) in patients at high risk of gastrointestinal bleeding, proton pump inhibitors are recommended [221-224].

RSC IA (LoE B, GoR 2)

Comments: The risk of gastrointestinal bleeding is increased in patients with a history of peptic ulcer disease or gastrointestinal bleeding, chronic use of nonsteroidal anti-inflammatory drugs or corticosteroids, as well as in the presence of at least 2 of the following features: age ≥ 65 years, dyspepsia, gastroesophageal reflux, Helicobacter pylori infection, or chronic alcohol consumption).

A potential attenuation of the antiplatelet effect of clopidogrel** (based on laboratory platelet reactivity assessments) has been noted when combined with omeprazole** or esomeprazole**, but not with pantoprazole or rabeprazole [188]. There is no evidence that these drug interactions adversely affect clinical treatment outcomes.

3.2.3.3. Alternative approaches to selecting the duration and composition of dual antiplatelet therapy (combination of ASA** with a platelet P2Y12 receptor blocker) during the first 12 months after STEMI

The balance between ischemic and bleeding risks plays a major role in determining the duration of dual antiplatelet therapy in patients with a history of STEMI. Criteria for elevated ischemic risk are outlined in Section 3.2.3.4, "Antithrombotic Therapy 12 Months After STEMI".

Validated scales play an important role in assessing bleeding risk. The most comprehensive and practically convenient assessment is provided by a consensus document developed in 2018 by 30 leading experts for patients scheduled for / undergoing PCI and/or requiring dual antiplatelet therapy – the Academic Research Consortium for High Bleeding Risk (ARC-HBR) scale. It includes 12 clinical criteria; high bleeding risk is defined by the presence of at least 1 major criterion or at least 2 minor criteria (Appendix G1) [225].

In patients with STEMI who underwent PCI without a high risk of ischemic events and who experienced no ischemic events during dual antiplatelet therapy (combination of ASA** with a platelet P2Y₁₂ receptor blocker), it is recommended to limit its duration to 3–6 months, switching to monotherapy with a platelet P2Y₁₂ receptor blocker to reduce the risk of bleeding and indirectly reduce the risk of ischemic events [226-232].

ESC IIaA (LoE A, GoR 2)

Comments: "Early" transition from dual antiplatelet therapy to antiplatelet monotherapy after PCI is most established when discontinuing ASA** and switching to ticagrelor** monotherapy at a dose of 90 mg twice daily [229, 230].

In patients with STEMI and a high risk of bleeding, it is recommended to consider switching from a combination of ASA** with a platelet P2Y₁₂ receptor blocker (dual antiplatelet therapy) to monotherapy with a platelet P2Y₁₂ receptor blocker or ASA** 1 month after initiating treatment [233, 234].

ESC IIbB (Level of Evidence B, Grade of Recommendation 2)

Comments: Such an "early" transition from dual antiplatelet therapy to antiplatelet monotherapy appears safest regarding ischemic events when ASA** is discontinued and patients are switched to ticagrelor** monotherapy at a dose of 90 mg twice daily following PCI; switching to clopidogrel** monotherapy in patients with STEMI who underwent PCI was associated with an increased risk of myocardial infarction in the STOPDAPT-2 ACS trial [234].

In patients with STEMI who underwent PCI and experienced no ischemic events during the first month of dual antiplatelet therapy, it is recommended to consider switching from a combination of ASA** with ticagrelor** or prasugrel to a combination of ASA** with clopidogrel** ("de-escalation" of dual antiplatelet therapy) to reduce the risk of bleeding and indirectly reduce the risk of ischemic events [235-238].

ESC IIbA (CoE B, LOE 2)

Comments: To date, unguided de-escalation of dual antiplatelet therapy by replacing ticagrelor** or prasugrel with clopidogrel** in the first month after ACS onset is not recommended. The approach to de-escalation of dual antiplatelet therapy based on laboratory data (taking into account residual platelet reactivity and CYP2C19 polymorphisms), studied in acute STEMI early after PCI, has no advantages over de-escalation without laboratory guidance.

3.2.3.4. Antithrombotic therapy 12 months after STEMI in patients with no indication for long-term oral anticoagulation

In STEMI survivors at high risk for ischemic events and low bleeding risk, who have not experienced bleeding during the first year of treatment, prolonged dual antithrombotic therapy (a combination of ASA** with a P2Y₁₂ platelet receptor blocker or rivaroxaban** at 2.5 mg twice daily) is recommended for a longer period to reduce the risk of death, recurrent MI, and overall ischemic events. During follow-up, the benefit-risk ratio of prolonged dual antithrombotic therapy should be regularly reassessed [239-243].

ESC IIaA (Level of Evidence B, Quality of Evidence 2)

Comments: A high risk of ischemic events is indicated by coronary artery disease combined with one of the following criteria: diabetes mellitus requiring treatment; history of recurrent MI; multivessel coronary artery disease; coexistence of coronary and peripheral atherosclerosis; premature coronary artery disease (age under 45 years); accelerated progression of coronary artery disease (two acute coronary events within the preceding 2 years); chronic systemic inflammatory disease (systemic lupus erythematosus, arthritis, human immunodeficiency virus carrier status); eGFR of 15–59 mL/min/1.73 m²; technical aspects of performed PCI: implantation of at least 3 stents, intervention on at least 3 lesions, total stent length greater than 60 mm, complex revascularization (left main coronary artery stenting, bifurcation stenting with at least 2 stents, chronic total occlusion stenting, stenting of the last patent vessel); history of stent thrombosis during antiplatelet therapy.

A high bleeding risk is indicated by a history of intracranial hemorrhage, ischemic stroke, or other intracranial pathology; recent gastrointestinal bleeding or anemia due to gastrointestinal blood loss; other gastrointestinal pathology associated with increased bleeding risk; hepatic impairment; hemorrhagic diathesis or coagulopathy; advanced age or frailty; CKD requiring dialysis or with an eGFR <15 mL/min/1.73 m².

In STEMI survivors at high risk for coronary complications who have not experienced bleeding during the first year of dual antiplatelet therapy, its extension with a combination of ASA** and a reduced dose of ticagrelor** (60 mg orally twice daily) for an additional 36 months is recommended to reduce the risk of ischemic events [242, 243].

ESC IIaB (LoE B, GoR 2)

Comments: In the PEGASUS-TIMI 54 trial, which demonstrated the feasibility of this approach, patients at high risk for coronary complications were defined as individuals aged ≥ 50 years with a history of MI combined with at least one of the following risk factors: age ≥ 65 years, diabetes mellitus requiring pharmacotherapy, history of two or more MIs, multivessel coronary atherosclerosis, or CKD with an eGFR less than 60 mL/min/1.73 m². The studied duration of combination therapy with ASA** and ticagrelor** at a dose of 60 mg twice daily is 36 months.

In STEMI survivors at high risk for thrombotic complications of atherosclerosis who have not experienced bleeding during the first year of treatment, long-term use of a combination of ASA** and rivaroxaban** at a dose of 2.5 mg orally twice daily is recommended to reduce the risk of ischemic events [239].

ESC IIaB (LoE B, GoR 2)

Comments: In the COMPASS trial [188], which demonstrated the feasibility of this approach, patients at high risk for thrombotic complications of atherosclerosis were defined as individuals with a history of MI or multivessel coronary atherosclerosis who were aged ≥ 65 years, had atherosclerotic lesions in other (non-coronary) vascular beds, or had at least two of the following risk factors: smoking, diabetes mellitus, history of mild chronic heart failure (CHF), history of non-lacunar ischemic stroke, or CKD with an eGFR less than 60 mL/min/1.73 m².

In STEMI survivors at 12 months, switching from ASA** monotherapy to P2Y₁₂ platelet receptor blocker monotherapy is recommended to further reduce the risk of ischemic events [244, 245].

ESC IIbA (Level of Evidence A, Quality of Evidence 1)

Comments: The additional benefit of clopidogrel** monotherapy is most evident in patients who underwent coronary stenting 1 year prior (the randomized controlled HOST-EXAM trial) [245]. Data supporting #ticagrelor** monotherapy at a dose of 90 mg twice daily (from the GLASSY analysis of the GLOBAL LEADERS trial) have also been published [246].

3.2.4. Organic nitrates

Due to the lack of evidence of a positive effect on prognosis, routine administration of organic nitrates via intravenous infusion, transdermally, or orally in STEMI is not recommended [247, 248].

ESC IIIB (LoE A, GoR 2)

Comment: In STEMI, nitrates are prescribed strictly by indication, primarily for post-infarction angina. Occasionally, nitrates are prescribed for heart failure, although angiotensin-converting enzyme inhibitors (ACE inhibitors) are better suited for this purpose. To prevent nitrate tolerance, they are administered intermittently: the time interval between the last dose of the day and the first dose the next day should be at least 12 hours (optimally 16 hours).

Intravenous infusion of nitrates (nitroglycerin** or isosorbide dinitrate**) is recommended for symptomatic treatment in STEMI patients with ongoing myocardial ischemia, hypertension, or heart failure in the absence of contraindications [14, 248-251].

ESC IC (Level of Evidence B, Grade of Recommendation 2)

Comment: The criterion for an adequately selected infusion rate (dose) during IV nitrate infusion is the level of systolic BP, which should be reduced by 10–15% in normotensive patients and by 25–30% in hypertensive patients, but not below 100 mm Hg. The usual initial infusion rate for nitroglycerin** is 10 mcg/min. If ineffective, the infusion rate is increased by 10–15 mcg/min every 5–10 minutes until the desired effect is achieved. If the target BP reduction cannot be achieved even after increasing the nitroglycerin** infusion rate up to 166 mcg/min, further dose escalation is pointless. The optimal duration of nitrate infusion is no more than 24–48 hours, as tolerance frequently develops thereafter. If hypotension develops, discontinuing the nitroglycerin** infusion is usually sufficient due to the drug's short half-life. Less frequently, standard measures to increase venous return to the heart are required (elevating the lower extremities; intravenous administration of 0.9% sodium chloride solution**, adrenergic and dopaminergic stimulants may be used).

Organic nitrates are not recommended in arterial hypotension, right ventricular myocardial infarction, or within 24 hours after taking sildenafil or vardenafil, or within 48 hours after tadalafil, due to the high risk of complications. Analgesics and caffeine-containing medications may be used for headache.

3.2.5. Beta-blockers

In STEMI patients with hypertension, persistent myocardial ischemia, and/or tachycardia, without signs of acute heart failure (AHF), intravenous administration of a beta-blocker (preferably metoprolol**) is recommended for ischemia control and prevention of ventricular arrhythmias in the absence of contraindications [252-256, 277].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

Comment: In STEMI patients without signs of AHF, intravenous administration of an initial dose of a beta-blocker is recommended, especially in the presence of hypertension, persistent myocardial ischemia, and/or tachycardia, followed by a transition to oral therapy. IV beta-blockers prevent the development of life-threatening ventricular arrhythmias [257].

Evidence indicates that the benefit of beta-blockers is greater the earlier therapy is initiated and the faster their action manifests. For drugs and IV dosing regimens, see Appendix A3.

In all STEMI patients without contraindications, oral administration of beta-blockers is recommended to reduce the risk of MI complications and improve prognosis [258].

ESC IIaB (LoE B, GoR 1)

Comment: Compelling evidence regarding the prognostic improvement with beta-blockers in NSTE-ACS patients was primarily obtained in the pre-reperfusion era. The benefit of routine beta-blocker administration in patients undergoing primary PCI has not been demonstrated by randomized clinical trials and systematic meta-analyses [253, 259–261]. The appropriateness of prescribing beta-blockers to patients with preserved left ventricular systolic function is a particularly pressing issue. Currently, several randomized trials are underway to evaluate the benefit of beta-blockers in patients with LVEF > 40% (BETAMI, DANBLOCK, REBOOT) and LVEF > 50% (REDUCE-AMI) [262–265]; their results may influence future guidelines.

At the same time, the results of some registries, retrospective studies, and meta-analyses suggest that the prescription of beta-blockers leads to an improved prognosis [266-270]. However, the accumulated evidence is ambiguous. For instance, not all registries indicate a clear benefit of prescribing beta-blockers to patients with preserved LVEF without heart failure [271-273].

In hemodynamically stable patients with STEMI, beta-blockers may be prescribed within the first 24 hours of symptom onset. In the early stages of STEMI, selecting an appropriate dose of the drug is of paramount importance; it should not be too high due to the risk of complications (primarily heart failure). The adequacy of the dose is usually judged by the achieved heart rate (HR), which should not fall below 44–46 beats per minute at night during rest.

Absolute contraindications to the use of beta-blockers, including in STEMI, comprise cardiogenic shock, severe chronic obstructive pulmonary disease in the acute stage, second- to third-degree atrioventricular (AV) block in patients without a functioning artificial cardiac pacemaker, and allergy (intolerance to drug components).

Relative contraindications to the use of beta-blockers include clinical manifestations of heart failure, evidence of low cardiac output, systolic BP < 100 mm Hg, HR < 60 beats per minute, PR interval prolongation > 0.24 s, history of obstructive pulmonary disease, and presence of risk factors for cardiogenic shock.

In patients with significant impairment of LV contractility, treatment should be initiated with the minimum doses of beta-blockers. After 24–48 hours following the resolution of severe bradycardia, arterial hypotension, severe heart failure, or AV block, careful titration of oral drug doses can be initiated. If baseline contraindications to beta-blockers are present, the possibility of their administration should be regularly reassessed. The prescription of beta-blockers with intrinsic sympathomimetic activity should be avoided.

The duration of beta-blocker therapy after uncomplicated MI is a subject of active debate. Some observational non-randomized studies indicate that the clinical benefit of beta-blocker therapy is limited to the first year following the index ACS. Two large-scale trials are currently underway: randomized clinical trials investigating the effect of beta-blocker withdrawal 6–12 months after uncomplicated ACS in patients with preserved LVEF: AβYSS (Beta Blocker Interruption After Uncomplicated Myocardial Infarction) and SMART-DECISION (Long-term Beta-blocker Therapy After Acute Myocardial Infarction) [274, 275].

To reduce the risk of death in patients with STEMI and heart failure and/or low (≤ 40%) LVEF, it is recommended to administer oral beta-blockers without intrinsic sympathomimetic activity [258, 276, 277].

ESC IA (LoE A, GoR 1)

Comment: Metoprolol** (group C07AB – selective beta-blockers) and carvedilol** (group C07AG – alpha- and beta-blockers) are considered studied in patients with STEMI.

3.2.6. Calcium channel blockers

Due to the lack of evidence of efficacy in patients with STEMI, routine prescription of calcium channel blockers is not recommended [278, 279].

ESC IIIA (LOCE B, LE 2)

Comment: Due to the potential for uncontrolled hypotension in patients with STEMI, the administration of short-acting nifedipine** (group C08CA – dihydropyridine derivatives) should be avoided [280].

Amlodipine** (group C08CA – dihydropyridine derivatives) may be prescribed to patients with post-infarction angina if beta-blockers and nitrates are insufficiently effective or if it is impossible to control hypertension with other means.

In case of intolerance to beta-blockers for myocardial ischemia control in patients with STEMI without heart failure, without low LVEF, and without other contraindications, it is recommended to consider the administration of verapamil** [278].

ESC IIb B (LoE B, GoR 2)

Comment: Verapamil** and diltiazem (group C08DA – phenylalkylamine derivatives) may be prescribed to patients with post-infarction angina if beta-blockers and nitrates are insufficiently effective or if it is impossible to control hypertension with other means. Verapamil** and diltiazem are sometimes used for heart rate control, and less frequently for the termination of supraventricular arrhythmias in cases of inefficacy of / contraindications to beta-blockers. Verapamil** or diltiazem may be used only in the absence of symptoms of heart failure and/or significant LV contractile dysfunction, sinoatrial and AV conduction disturbances, and bradyarrhythmias. Concomitant administration of verapamil** or diltiazem with a beta-blocker is highly undesirable.

3.2.7. Renin-angiotensin-aldosterone system blockers

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)

To prevent LV dysfunction, heart failure, and death, it is recommended to use ACE inhibitors in all patients with STEMI who have no contraindications [281].

ESC IIaA (LOCE B, LE 2)

To reduce the risk of death and the development/progression of heart failure, it is recommended to initiate early (within the first 24 hours of STEMI) administration of ACE inhibitors in patients with heart failure, low (≤ 40%) LVEF, diabetes mellitus, or anterior myocardial infarction [281, 282].

ESC IA (LoE A, GoR 1)

Comment: In hemodynamically stable patients, the administration of ACE inhibitors within the first 24 hours from symptom onset is safe [283]. The dose of ACE inhibitors should be gradually increased to the recommended (target) dose, which, according to clinical trials, provides a positive effect on prognosis, or if this is not possible, to the maximum tolerated dose (Appendix A3).

Contraindications to initiating ACE inhibitors: systolic BP < 100 mm Hg, severe impairment of renal filtration function, hyperkalemia, bilateral renal artery stenosis (or renal artery stenosis of a single kidney), pregnancy, individual intolerance.

In patients with STEMI presenting with heart failure and/or low (≤ 40%) LVEF or hypertension, in case of ACE inhibitor intolerance, it is recommended to use ARBs, preferably valsartan, for the treatment of heart failure, reduction of mortality risk, and prevention of heart failure progression [284].

ESC IB (LoE B, LoR 2)

Comment: The starting dose of valsartan is 20 mg twice daily ; if well tolerated, the drug dose is gradually increased up to 160 mg twice daily.

In patients with STEMI and low (≤ 40%) LVEF and/or signs of pulmonary congestion, it is recommended to prescribe sacubitril/valsartan** to reduce the risk of cardiovascular death and hospitalization for heart failure [285-297].

ESC IIaB (LOCE B, LE 2)

Comment: According to the results of the PARADISE-MI trial, sacubitril/valsartan ** (group C09DX – angiotensin II receptor blockers in combination with other drugs) was non-inferior to ramipril** in its effect on the rate of death or hospitalization for worsening heart failure when administered in the early period (from 12 hours to 7 days) of STEMI [286-297]. In the PARADIGM-HF trial, sacubitril/valsartan ** demonstrated superior efficacy compared to enalapril** regarding the reduction of the risk of death or hospitalization for worsening heart failure in patients with chronic heart failure and reduced LVEF [285].

Aldosterone antagonists

To reduce the risk of mortality and heart failure progression in patients with STEMI and low (≤ 40%) LVEF combined with heart failure or diabetes mellitus, it is recommended to add an aldosterone antagonist, preferably eplerenone, to a beta-blocker and an ACE inhibitor, provided there is no significant impairment of renal filtration function and no hyperkalemia [298].

ESC IIaB (LOCE A, LE 2)

Comment: It is preferable to prescribe eplerenone within the first 24 hours of MI onset [299]. There is evidence of a reduced risk of death with the use of aldosterone antagonists, including spironolactone** (group C03DA – aldosterone antagonists), in STEMI patients in the absence of contraindications and regardless of the presence of heart failure and low LVEF [300, 301]. With this approach, it is preferable to administer the aldosterone antagonist within 72 hours of STEMI onset.

Contraindications to aldosterone antagonists: blood creatinine level in men > 220 µmol/L, in women > 175 µmol/L, and blood potassium concentration > 5 mmol/L. During treatment with aldosterone antagonists, blood creatinine and potassium levels should be monitored. If blood potassium exceeds 5.5 mmol/L, the drugs are discontinued. It is recommended to maintain blood potassium concentration within 4.0–5.0 mmol/L.

3.2.8. Lipid-lowering therapy

To reduce the cumulative risk of recurrent ischemic events in patients with STEMI, regardless of baseline cholesterol (C) levels, it is recommended to initiate or continue treatment with a high-dose 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (HMG-CoA reductase inhibitor) during hospitalization, provided there are no contraindications [302-306].

ESC I A (LoE A, GoR 1)

Comments: Initiation (first dose) of a high-dose HMG-CoA reductase inhibitor (syn.: statin) is recommended within the first day of hospitalization for a STEMI patient and as early as possible. If PCI is performed, the first dose of the HMG-CoA reductase inhibitor is recommended before the procedure to reduce the likelihood of cardiovascular complications and contrast-induced nephropathy following PCI [307-308].

Both the appropriateness of administration and the initial dose of the HMG-CoA reductase inhibitor in STEMI are not determined by the total cholesterol and its fractions; therefore, there should be no delay in initiating the HMG-CoA reductase inhibitor while waiting for blood biochemistry results.

In patients with STEMI undergoing primary PCI, there is abundant evidence of an additional reduction in the risk of ischemic events and even death with high-dose HMG-CoA reductase inhibitors initiated prior to PCI (compared to initiating HMG-CoA reductase inhibitors at later stages of hospitalization) [307-315].

HMG-CoA reductase inhibitor therapy is generally well tolerated, with the incidence of serious adverse effects not exceeding 2%. Myalgia and muscle weakness may occur, predominantly in the first weeks after starting therapy, and usually resolve quickly after discontinuing the HMG-CoA reductase inhibitor. Rhabdomyolysis with a more than 10-fold increase in creatine kinase is extremely rare. An asymptomatic 3-fold or greater increase in transaminases may occur, requiring a dose reduction or drug discontinuation with subsequent monitoring of liver transaminase activity. It should be kept in mind that in the acute phase of STEMI, elevated transaminases are caused by cardiomyocyte necrosis and do not constitute a reason to withhold HMG-CoA reductase inhibitors.

Main contraindications for prescribing HMG-CoA reductase inhibitors: hypersensitivity; active liver disease or unexplained elevations in plasma liver transaminases exceeding 3 times the upper limit of normal; women of childbearing potential not using adequate contraception; pregnancy; lactation period.

It is recommended to use HMG-CoA reductase inhibitors with the most pronounced lipid-lowering effect, specifically atorvastatin** at a daily dose of 40–80 mg or rosuvastatin at a daily dose of 20–40 mg [315, 316].

To further reduce the cumulative risk of ischemic events in patients with STEMI during hospitalization, it is recommended to consider initiating combined therapy with a high-dose HMG-CoA reductase inhibitor and ezetimibe (regardless of baseline cholesterol levels and fractions and prior HMG-CoA reductase inhibitor therapy) [317].

ESC IIbB (Level of Evidence B, Grade of Recommendation 2)

Comment: This recommendation is based on the results of the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study. In the early stage (first 10 days) of ACS, ezetimibe was added to previous statin therapy or prescribed simultaneously with statins in statin-naive patients (two-thirds of patients) compared with statin monotherapy. Ezetimibe treatment was shown to be safe and provided long-term benefits regarding cardiovascular outcomes [317].

In patients with a history of STEMI, it is recommended to maintain an LDL-C level < 1.4 mmol/L while achieving a reduction of at least 50% from baseline values to ensure the maximum effect in reducing the risk of recurrent ischemic events [317-321].

ESC IA (LoE A, GoR 1)

Comments: Blood LDL-C levels should be measured 4–6 weeks after initiating treatment, after changing the dose, or after adding a new lipid-lowering drug to assess therapy efficacy, determine the need for a dose increase, and/or add lipid-lowering drugs with a different mechanism of action (ezetimibe and/or alirocumab** or evolocumab** (group C10AX – other lipid-lowering agents) or inclisiran) [317, 319].

In patients with STEMI who have experienced another vascular event (in any vascular bed) within the preceding 2 years in addition to the current STEMI, an LDL-C target level of < 1.0 mmol/L is recommended to further reduce the risk of recurrent ischemic events [322, 323].

ESC IIbB (Level of Evidence C, Grade of Recommendation 5)

In patients who, at the time of STEMI presentation, were already taking a maximum tolerated dose of an HMG-CoA reductase inhibitor and ezetimibe, but present with LDL-C levels above target, early administration (during hospitalization for the current coronary event) of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor – alirocumab**, evolocumab**, or inclisiran – is recommended in addition to the maximally tolerated HMG-CoA reductase inhibitor and ezetimibe [324-328].

ESC IIaC for alirocumab and evolocumab,

RSC IIaC for inclisiran (LoE B, GoR 2)

Comment: The clinical efficacy of inclisiran has been demonstrated in meta-analyses of relatively small studies, which included patients with a history of myocardial infarction. A large-scale study, ORION-4, is currently underway to investigate the effect of inclisiran on cardiovascular events, with results expected in 2025.

In the presence of a significant increase (> 4.0 mmol/L) in LDL-C levels in patients with STEMI, early initiation (during hospitalization for the current coronary event) of an HMG-CoA reductase inhibitor and ezetimibe, preferably in a single tablet or capsule, is recommended [329].

RSC IIaA (LoE A, GoR 1)

In the presence of an extremely high increase (> 5.0 mmol/L) in LDL-C levels in patients with STEMI, early initiation (during hospitalization for the current coronary event) of a maximally tolerated dose of an HMG-CoA reductase inhibitor + ezetimibe + a PCSK9 inhibitor (alirocumab**, evolocumab**, or inclisiran) is recommended [330-332].

RSC IIA (LoE A, GoR 1)

If a patient with a history of STEMI maintains an LDL-C concentration above the target level despite receiving a maximally tolerated dose of an HMG-CoA reductase inhibitor, it is recommended to add ezetimibe to the HMG-CoA reductase inhibitor to further reduce blood LDL-C and the risk of ischemic events, including the use of an HMG-CoA reductase inhibitor/ezetimibe fixed-dose combination in a single tablet or capsule [317].

ESC IIaB (LoE B, GoR 2)

Comment: This recommendation applies to patients in whom ezetimibe was not prescribed during hospitalization for STEMI in accordance with the inpatient phase guidelines.

If a patient with a history of STEMI maintains an LDL-C concentration above the target level despite receiving a maximally tolerated dose of an HMG-CoA reductase inhibitor combined with ezetimibe, it is recommended to add alirocumab**, evolocumab**, or inclisiran for further reduction of blood LDL-C and ischemic event risk [320, 321].

ESC IB for alirocumab and evolocumab,

RSC IB for inclisiran (LoE A, GoR 2)

Comment: If LDL-C levels remain significantly elevated (> 2.5 mmol/L) despite maximally tolerated HMG-CoA reductase inhibitor therapy, adding alirocumab**, evolocumab**, or inclisiran** without prior ezetimibe use may be considered.

In patients with STEMI or a history of STEMI with HMG-CoA reductase inhibitor intolerance, it is recommended to consider the use of ezetimibe and/or a PCSK9 inhibitor (alirocumab**, evolocumab**, or inclisiran) to achieve target LDL-C levels [320, 321].

ESC IIbB for alirocumab and evolocumab,

RSC IIbB for inclisiran (LoE C, GoR 5)

3.3. Other treatment

In patients with STEMI and a blood glucose concentration above 10 mmol/L, it is recommended to use hypoglycemic agents for glycemic control [333-335].

ESC IIaC (LoE B, GoR 2)

Comments: The target blood glucose and glycated hemoglobin levels in the management of STEMI are not defined and should be chosen taking into account comorbidities. Hypoglycemia should be avoided.

To achieve target glycemia levels in patients with STEMI, an individualized approach to the choice of glucose-lowering drugs is recommended. The presence of type 2 diabetes mellitus in a patient with STEMI is not a mandatory indication for switching to insulin therapy; many can continue taking oral glucose-lowering drugs. If a patient with type 2 diabetes mellitus requires insulin, switching to oral glucose-lowering agents is recommended after stabilization.

Patients with STEMI without impaired consciousness and other serious complications who are able to eat independently can receive subcutaneous insulin therapy, provided that it maintains the target glycemic range and avoids hypoglycemia. The method of choice for rapid and controllable achievement of carbohydrate metabolism compensation is continuous intravenous infusion of insulins and rapid-acting analogs, combined with intravenous dextrose** infusion if necessary (Appendix A3. Intravenous insulin therapy in STEMI ).

In patients with STEMI without diabetes and with diabetes out of glycemic control, it is not recommended to use simultaneous infusion of insulins and dextrose**, or simultaneous infusion of insulins, dextrose**, and potassium chloride** due to the lack of evidence of a positive effect on mortality and the incidence of non-fatal complications [14, 340].

ESC IIIC (CGR C, LOR 5)

In patients with STEMI, it is not recommended to use non-steroidal anti-inflammatory and antirheumatic drugs (except for low doses of ASA** as an antiplatelet agent and moderate doses of ASA** for the treatment of pericarditis) due to their adverse effect on prognosis [341, 342, 521].

ESC IIIB (LOC A, LOE 1)

Comments: It is recommended to discontinue non-steroidal anti-inflammatory and antirheumatic drugs and/or not initiate their use upon hospital admission for STEMI.

In patients with STEMI and anemia without signs of ongoing bleeding and hemodynamic instability, the appropriateness of blood transfusion is recommended to be considered when the hematocrit drops below 25% and/or hemoglobin below 70 g/L to reduce the risk of transfusion-related complications and the potential adverse effect of blood transfusions on prognosis [14].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

In patients with STEMI who are in a coma after out-of-hospital or in-hospital cardiac arrest, it is recommended to monitor body temperature, including continuous core temperature monitoring and active prevention of fever (>37.7°C), for at least 72 hours to prevent complications [343-353].

ESC IB (LoE B, GoR 3)

If body temperature cannot be controlled medically in comatose patients with STEMI after cardiac arrest, it is recommended to consider targeted temperature management using special surface or endovascular devices with continuous feedback targeting a temperature of 32-37°C, if technically feasible [343-356].

ESC IIaB (LOC B, LOE 2)

3.4. Complications

3.4.1. Acute heart failure

Acute heart failure (AHF) may occur as a complication of STEMI or reflect decompensation of pre-existing chronic heart failure during myocardial ischemic injury. The onset of AHF in patients with STEMI increases the risk of other complications: impaired renal filtration function, respiratory failure, pneumonia, and increases the likelihood of death.

Left ventricular (LV) myocardial dysfunction can always be diagnosed in a patient with AHF. The degree of LV myocardial dysfunction is an independent predictor of mortality in a patient with STEMI. Early detection of impaired myocardial function by echocardiography allows for the timely initiation of therapeutic measures to prevent the development of heart failure.

The development of AHF in patients with STEMI worsens short- and long-term prognosis. The Killip classification is used in patients with STEMI to assess the severity of AHF and evaluate short-term prognosis.

The primary therapeutic strategy in patients with STEMI complicated by AHF is emergency myocardial revascularization to limit ischemic injury.

In patients with STEMI and AHF, it is recommended to continuously monitor vital signs—at least heart rate, blood pressure, SpO₂, and urine output—until hemodynamic stabilization [14, 354, 357].

RSC IIaC (LOC C, LOE 5)

In patients with STEMI upon the appearance of signs of AHF, it is recommended to urgently perform an echocardiogram to assess LV myocardial contractility, valve status, and screen for mechanical complications of MI [14, 50-52].

RSC IIaC (LOC C, LOE 5)

Comment: If an echocardiogram has already been performed, a repeat echocardiogram is recommended to monitor global and regional LV contractility and to detect/exclude mechanical complications of STEMI. Serial echocardiographic monitoring is also recommended to assess the efficacy and safety of ongoing therapy.

To assess the presence and severity of AHF, it is recommended to use the Killip classification in all cases of STEMI [14, 358, 359].

ESC IIaC (LoE C, GoR 5)

Comment: The Killip classification is presented in Appendix A3. Killip classification of acute heart failure in myocardial infarction.

3.4.1.1. Pulmonary edema

Against the background of a marked decrease in LV systolic myocardial function and/or mechanical complications (mitral valve dysfunction, ventricular septal rupture), pulmonary capillary wedge pressure increases, leading to fluid extravasation from the intravascular bed into the lung tissue. Interstitial and alveolar pulmonary edema are distinguished. Diagnosis of pulmonary edema is straightforward in most cases due to the typical clinical presentation. The most characteristic signs on examination are: tachycardia, tachypnea, forced elevated posture (orthopnea). Lung auscultation reveals "congestive" fine crackles. Decreased blood oxygenation is recorded. The diagnosis can be confirmed by chest radiography and lung ultrasound. Patients with STEMI and AHF (especially with pulmonary edema) exhibit decreased blood saturation.

It is recommended to administer supplemental oxygen (oxygen therapy) to a patient with STEMI and AHF via a face mask when SpO₂is below 90% or PaO₂ is below 60 mmHg to correct hypoxemia [14, 171, 172].

ESC IC (RR S, ELD 5)

Comment: During prolonged oxygen administration (oxygen therapy), periodic assessment of arterial and venous blood gas composition (acid-base balance and blood gases analysis) is recommended.

Routine oxygen therapy in patients without hypoxemia (SpO₂greater than or equal to 90%) is not recommended.

To improve the efficacy of heart failure treatment in patients with STEMI presenting with severe respiratory failure (SpO₂ below 90% and tachypnea above 25 breaths per minute), it is recommended to consider non-invasive positive pressure ventilation via mask (continuous or bilevel ventilation) [360-362].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

Comment: The use of non-invasive ventilation is advisable via a mask (continuous positive airway pressure—CPAP or biphasic positive airway pressure—BiPAP). Positive airway pressure protects alveoli from collapsing during expiration and maintains respiratory surface area in pulmonary edema. As a result, the work of breathing is reduced, pulmonary gas exchange is improved, and intrathoracic pressure increases, decreasing preload and afterload. Evidence suggests that non-invasive mechanical ventilation should be considered as soon as possible, as it reduces the need for endotracheal intubation and invasive mechanical ventilation.

The primary mode of non-invasive ventilation in this clinical situation is CPAP, although BiPAP is advisable in patients with concomitant bronchopulmonary disease and hypercapnia.

During non-invasive mechanical ventilation, periodic assessment of arterial and venous blood gas composition is recommended.

If a patient with STEMI has respiratory failure accompanied by severe hypoxemia, hypercapnia, and acidosis, and if oxygen therapy and non-invasive ventilation are ineffective, it is recommended to perform endotracheal intubation and initiate invasive mechanical ventilation [360].

ESC IC (RR S, ELD 5)

In patients with STEMI and AHF with signs of fluid retention, it is recommended to intravenously administer loop diuretics [363, 364].

ESC IC (RR S, ELD 5)

Comment: Intravenous bolus administration of furosemide** (group C03CA – sulfonamides) is used. The recommended initial dose is 40 mg. In cases of a full-blown picture of acute alveolar pulmonary edema, signs of fluid retention in the body, and severe impairment of renal filtration function, the initial dose of furosemide** may be increased to 60–80 mg. If the initial dose is insufficiently effective upon repeated administration of furosemide**, the dose may be increased twofold or more.

In patients with STEMI and acute heart failure with signs of fluid retention/congestion and no adequate response to escalating doses of loop diuretics, in order to stabilize the condition, it is recommended to consider the advisability of prescribing a combination of loop diuretics with thiazide diuretics (thiazides) [364].

ESC IIa B (LoE C, GoR 5)

In patients with STEMI and acute heart failure with signs of congestion in the pulmonary circulation and a systolic BP of 110 mm Hg or higher, and especially with high BP levels, to reduce the severity of acute heart failure symptoms, it is recommended to consider the possibility of IV infusion of vasodilators (group C01D – vasodilators used in cardiac diseases) [365-369].

ESC IIb B (LoE C, GoR 5)

Comment: In patients with pulmonary edema and elevated BP, nitroglycerin** is the first-line drug. If baseline systolic BP is ˂ 90 mm Hg or there are signs of hypoperfusion, as well as right ventricular involvement, the administration of nitroglycerin** is contraindicated.

Routine administration of opioid drugs in the development of acute heart failure in a patient with STEMI is not recommended, except for patients with severe pain syndrome or agitation [370-373].

ESC IIIC (LoE C, GoR 4)

Comment: A retrospective analysis showed that the use of opioids is associated with an increased need for mechanical ventilation, longer hospital stays, and an increase in adverse in-hospital outcomes.

3.4.1.2. Cardiogenic shock

Cardiogenic shock is the most severe form of acute heart failure in patients with STEMI. Cardiogenic shock is a life-threatening condition caused by a sharp decrease in cardiac output and manifested by signs of pronounced organ and tissue hypoperfusion and tissue hypoxia, which is clinically manifested by decreased skin temperature and marbling, reduced urine output rate (˂ 40 mL/h), and alterations in mental status and consciousness.

There are 3 main pathogenetic variants of cardiogenic shock:

True cardiogenic shock associated with a decrease in left ventricular contractility (hypokinetic).
Shock due to relative and absolute hypovolemia. A close variant to this is reflex shock associated with a reaction to a pain attack.
Arrhythmic variant — hemodynamic disturbances against the background of severe tachy- and bradyarrhythmias (see section "Arrhythmias").

The frequency of various causes of cardiogenic shock, according to the SHOCK registry: 79% – decreased left ventricular contractility, 7% – acute mitral regurgitation, 4% – ventricular septal rupture, 2% – isolated right ventricular failure, 1.4% – tamponade, 7% – other causes (catheterization complications, overdose or unjustified prescription of beta-blockers, slow calcium channel blockers, etc.) [157]. The main clinical sign of cardiogenic shock is persistent hypotension (systolic BP ≤ 90 mm Hg) refractory to fluid therapy and accompanied by signs of acute multiorgan failure as a result of hypoperfusion. Objectification of hemodynamic parameters using invasive techniques, including Swan-Ganz catheter placement, is not currently considered routinely mandatory, but in controversial and complex cases, it allows obtaining a number of valuable data.

Hemodynamic criteria for true shock:

1. Hypotension — systolic BP < 80–90 mm Hg with a mean BP ˂ 70 mm Hg. The formula for calculating mean BP = 1/3 systolic BP + 2/3 diastolic BP.

2. A sharp decrease in cardiac index (CI) according to invasive hemodynamic monitoring:

<1.8 L/min/m² without vasoactive therapy;
<2.0–2.2 L/min/m² with vasoactive therapy.

3. Increased ventricular filling pressures:

Left ventricular end-diastolic pressure (LVEDP) > 18 mm Hg;
Right ventricular end-diastolic pressure > 10 mm Hg.

From the perspective of invasive hemodynamics, cardiogenic shock is characterized by a reduced CI, increased systemic vascular resistance (SVR), and pulmonary capillary wedge pressure (PCWP). However, these parameters may vary. Based on invasive hemodynamic monitoring data, hemodynamic variants of cardiogenic shock can be distinguished (Appendix A3. Hemodynamic variants of cardiogenic shock)

Patients with STEMI and cardiogenic shock are indicated for the placement of a central venous catheter (catheterization of the subclavian and other central veins) for the administration of medications, primarily vasoactive drugs, and measurement of mixed venous saturation and central venous pressure (CVP) (Appendix A3. Monitoring parameters in a patient with cardiogenic shock) [14, 430, 442, 448].

RSC IIaC (LOC C, LOE 5)

In patients with STEMI and cardiogenic shock, a clinical examination at least once an hour and monitoring of vital functions are recommended to determine clinical severity and response to treatment, with the frequency recommended in Appendix A3. Monitoring parameters in a patient with cardiogenic shock [14, 430, 442, 448].

RSC IIaC (LOC C, LOE 5)

Depending on clinical severity and response to treatment, the following stages of cardiogenic shock are distinguished: preshock, full-blown cardiogenic shock, and refractory cardiogenic shock (Appendix A3. Stages of cardiogenic shock depending on clinical severity and response to treatment), which can also be divided into five stages according to the Society for Cardiovascular Angiography and Interventions (SCAI) classification (Appendix A3. Stages of cardiogenic shock according to the Society for Cardiovascular Angiography and Interventions (SCAI) classification) [374]:

Reperfusion therapy and myocardial revascularization are the basis of treatment for cardiogenic shock in STEMI.

Treatment of true cardiogenic shock

Upon the appearance of signs of acute left ventricular failure / cardiogenic shock in patients with STEMI, urgent myocardial revascularization is recommended if it has not been performed previously or was incomplete [157, 375, 376].

ESC IА (LOCR B, LOE 2)

Comment: See also section 3.1.7. "Reperfusion treatment in patients with cardiogenic shock and sudden cardiac arrest".

In patients with STEMI and cardiogenic shock, it is recommended to consider performing invasive central hemodynamic monitoring to control the efficacy and safety of treatment, as well as pulmonary artery catheterization to clarify the cause of cardiogenic shock, provided physical and technical capabilities are available [137].

RSC IIaC (LOC C, LOE 5)

In patients with STEMI and acute heart failure with a systolic BP of less than 90 mm Hg and signs of hypoperfusion, to eliminate hemodynamic instability, it is recommended to consider prescribing inotropic drugs [377].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

Comment: Dopamine** infusion (group C01CA – adrenergic and dopaminergic agents) is started at a rate of 5 mcg/kg/min, then, depending on the hemodynamic response, it can be increased to 15-20 mcg/kg/min. Dobutamine** (group C01CA – adrenergic and dopaminergic agents) is administered at an initial rate of 2–10 mcg/kg/min; if necessary, the rate can be increased to 20 mcg/kg/min. Norepinephrine** (group C01CA – adrenergic and dopaminergic agents) is started at a rate of 2 mcg/kg/min, and the rate is increased if necessary. If the effect is insufficient, drugs can be combined, primarily dobutamine** and norepinephrine**.

In patients with STEMI and acute heart failure who have been on long-term beta-blockers prior to STEMI development, and in patients with inadequate urine output in response to repeated IV diuretic administration, levosimendan** (group C01CX – other cardiotonic agents) may be considered as an alternative to adrenergic agents. Levosimendan** infusion is initiated with a loading dose (6 mcg/kg) administered as an IV bolus over 10 minutes, followed by a continuous IV infusion at a dose of 0.1 mcg/kg/min and titrated up to 0.2 mcg/kg/min (until systolic BP is stabilized for at least 3 hours). The recommended infusion duration is 24 hours. In patients with systolic BP < 100 mm Hg and/or diastolic BP < 60 mm Hg, the initial bolus of levosimendan** is usually omitted to prevent hypotension.

In all patients with STEMI and acute heart failure with a systolic BP of less than 90 mm Hg without signs of hypoperfusion, the administration of inotropic drugs is not recommended, since the potential benefit is less than the potential risk [377-379].

ESC IIIC (LoE C, GoR 4)

In patients with STEMI and cardiogenic shock, to eliminate hemodynamic instability and maintain perfusion of vital organs in the presence of arterial hypotension, it is recommended to consider the administration of vasopressors, with a preference for norepinephrine** (intravenous infusion) over dopamine** due to a lower incidence of adverse effects of norepinephrine** [380-382].

ESC IIbB (LE A, LoE 2)

In patients with STEMI and cardiogenic shock, if technically feasible, it is recommended to consider the use of external and internal mechanical circulatory support devices: intra-aortic balloon counterpulsation, left atrial-to-aortic continuous-flow ventricular assist device, left ventricular-to-aortic continuous-flow ventricular assist device, left ventricular-to-aortic pulsatile-flow ventricular assist device, extracorporeal membrane oxygenation (ECMO) [14, 383-388].

ESC IIaC (LoE C, GoR 5)

Comment: This approach is used as a temporary measure (“bridge”) to stabilize patients preparing for revascularization, surgical correction of the causes of shock, heart transplantation, or another intermediate decision.

In patients with STEMI and cardiogenic shock, it is recommended to consider the use of intra-aortic balloon counterpulsation (IABC) if this treatment serves as a bridge to revascularization, heart transplantation, implantation of a long-term mechanical circulatory support system, or another intermediate decision [14, 385-389].

ESC IIbC (LoE C, GoR 5)

Routine use of IABC in patients with STEMI and cardiogenic shock is not recommended unless this treatment is a bridge to another type of treatment for acute heart failure and/or its underlying cause [14, 385, 386, 388].

ESC IIIC (Level of Evidence C, Level of Certainty 5)

Treatment of Hypovolemic Cardiogenic Shock

All patients with STEMI and suspected hypovolemic shock are recommended to undergo echocardiography to identify potential causes of hypovolemia (right ventricular infarction, cardiac tamponade, etc.) and assess the functional state of the heart [14, 137, 230].

ESC IIbC (Level of Evidence C, Level of Certainty 5)

In patients with STEMI and signs of hypovolemic shock, to ensure efficacy and safety, treatment is recommended to be carried out under the control of central hemodynamics parameters, and if technically feasible, with pulmonary artery wedge pressure (PAWP) measurement using a Swan-Ganz catheter (balloon catheter for pulmonary artery, standard***) [137, 390].

ESC IIbC (Level of Evidence C, Level of Certainty 5)

Comment: If PAWP measurement is not feasible, central venous pressure (CVP) can be assessed, but it should be borne in mind that in patients with STEMI, CVP values may not reflect left ventricular end-diastolic pressure (LVEDP).

In patients with STEMI and hypovolemic shock, fluid resuscitation to normalize blood pressure is recommended to begin with the intravenous administration of 200–250 ml of 0.9% sodium chloride solution**, infused over 5–10 minutes. If arterial hypotension persists, repeated administration of 0.9% sodium chloride solution** is recommended [137, 390].

ESC IIb C (Level of Evidence C, Level of Certainty 5)

Comment: The volume of fluid infused into the patient may reach several liters. Once blood pressure stabilizes and diuresis appears, the infusion is discontinued. If fluid administration is ineffective, treatment with adrenergic and dopaminergic agonists—dopamine** or dobutamine**—is administered concurrently.

3.4.2. Cardiac rhythm and conduction disturbances

3.4.2.1. Ventricular arrhythmias

In patients with STEMI complicated by hemodynamically significant ventricular tachycardia (VT) or ventricular fibrillation (VF), to restore circulation, immediate external electrical cardioversion (defibrillation) is recommended, respectively [14, 47].

RSC IC (LoE C, GoR 5)

In patients with STEMI and recurrent VT/VF, to eliminate ischemia as a potential cause of arrhythmias (in cases where revascularization has not been performed previously or was incomplete), emergency and/or complete revascularization is recommended (see the section Invasive Treatment of the Disease) [14, 47, 390, 391].

ESC IC (RR S, ELD 5)

Comment: Complete revascularization is particularly important when VF/VT develops in patients with STEMI and reduced global left ventricular (LV) systolic function. In the absence of effective cardiac activity, CPR and PCI may be performed concurrently with mechanical chest compressions using special devices—automatic external chest compression devices.

In patients with STEMI presenting with polymorphic VT or VF, in the absence of contraindications, intravenous administration of a beta-blocker and/or amiodarone** is recommended [392-395].

ESC IB (LoE B, GoR 3)

Comment. Early intravenous administration of beta-blockers is not recommended in the presence of hypotension, cardiogenic shock, bradyarrhythmia, or suspected involvement of the right ventricular ischemia zone. Prior to initiating beta-blocker therapy, LV contractility should be assessed by echocardiography; in cases of reduced LV contractility, the use of low doses or delaying therapy initiation is advisable. When selecting a specific beta-blocker, its route of administration, and dose titration, it is recommended to regularly reassess the patient's condition, therapy tolerance, achieved effect, and the presence of limiting factors: heart rate < 50 bpm, blood pressure < 90 mm Hg, LV ejection fraction by echocardiography, etc.

If the QT interval duration increases to > 500 ms, the administration of amiodarone** (ATC group C01BD – antiarrhythmic drugs, class III) must be discontinued.

In patients with STEMI presenting with recurrent VT and lack of response to therapy with beta-blockers and amiodarone**, or in cases where these drugs cannot be prescribed, intravenous administration of lidocaine** is recommended [14, 392].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

Comment: Lidocaine** – ATC group Antiarrhythmic drugs, C01BB; class IB.

In patients with STEMI and recurrent life-threatening VT who do not respond to therapy with beta-blockers and amiodarone**, it is recommended to consider sedation or general anesthesia to reduce sympathetic tone [14, 47].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

Comment: This method should only be considered in selected patients, as the use of sedation/general anesthesia may increase the risk of inflammatory and thrombotic complications.

In patients with STEMI who develop VT and/or VF, monitoring, identification, and correction of electrolyte disorders (primarily hypokalemia and hypomagnesemia) are recommended [137, 396].

RSC IIaC (LOC C, LOE 5)

Comment: To detect electrolyte imbalances, blood potassium testing, serum total magnesium testing, and acid-base status and blood gas analysis are performed.

Potassium supplementation is necessary if blood potassium levels are below 4 mmol/L. Approximately 40% of patients are found to have a concurrent decrease in magnesium concentration along with hypokalemia. These patients are at a particularly high risk for VF. Therefore, it is advisable to determine magnesium levels in STEMI patients. If the magnesium concentration is below 0.83 mmol/L (2 mg/dL), correction should be performed.

Intravenous potassium chloride may be used to correct hypokalemia, and intravenous magnesium sulfate is used to correct magnesium levels; the dose, regimen, and duration are determined individually, depending on blood electrolyte concentrations, acid-base balance parameters, and the clinical situation.

In patients with STEMI presenting with recurrent VT/VF and hemodynamic instability refractory to medical correction, mechanical circulatory support is recommended to be considered, provided physical and technical capabilities are available [392].

ESC IIbC (LoE C, GoR 5)

In patients with STEMI and VT and/or VF recurring despite revascularization and optimal medical therapy, radiofrequency ablation of arrhythmogenic zones in the subacute phase followed by ICD implantation is recommended [14].

ESC IIaC (LoE C, GoR 5)

In patients with a history of STEMI (at least 6 weeks ago) who, despite optimal medical therapy (for 3 months or longer), have symptomatic HF (NYHA functional class II–III) and an LVEF ≤ 35%, with a life expectancy of at least 1 year and preserved functional status, ICD implantation is recommended (combined with cardiac resynchronization therapy if indicated) [397, 398, 522].

ESC IA (CGR B, LOR 1)

Comment: Criteria for determining life expectancy have not been established. It is recommended to make decisions individually, taking into account the specifics of each clinical case. Indicators of a short life expectancy include, in particular, late-stage malignant neoplasms with metastases unresponsive to ongoing treatment, and palliative treatment for severe heart failure.

In patients with STEMI presenting with sustained VT or VF occurring later than 48 hours from STEMI onset and in the absence of evidence for ongoing myocardial ischemia, ICD implantation is recommended, provided technical capabilities are available [392].

ESC IA (Level of Evidence C, Grade of Recommendation 5)

In patients with polymorphic VT or VF occurring later than 48 hours after STEMI onset, in the presence of incomplete myocardial revascularization and baseline low LVEF, it is recommended to consider ICD*** implantation or the use of a wearable cardioverter-defibrillator (WCD) within up to 40 days of STEMI development [14].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

In patients with STEMI, treatment of asymptomatic and hemodynamically insignificant ventricular arrhythmias with antiarrhythmic drugs is not recommended [14, 392].

ESC IIIC (LoE C, GoR 5)

In patients with STEMI, prophylactic administration of antiarrhythmic drugs other than beta-blockers is not recommended [392].

ESC IIIB (LoE C, GoR 5)

3.4.2.2. Atrial fibrillation

Atrial fibrillation (AF) is the most common type of supraventricular arrhythmia in patients with STEMI. AF is generally well tolerated, but some patients may develop hemodynamic instability due to rapid ventricular response. In hemodynamically stable patients, specific treatment is usually not required, except for anticoagulant prophylaxis of thromboembolic complications.

In patients with STEMI and new-onset AF with hemodynamic instability, immediate external electrical cardioversion is recommended [14].

ESC IC (LoE C, SoR 5)

In hemodynamically unstable patients with STEMI and new-onset AF, intravenous amiodarone** is recommended to support external electrical cardioversion and reduce the risk of AF recurrence [14, 399, 400].

ESC IC (LoE C, GoR 5)

Comment: If the QT interval increases > 500 ms, amiodarone** infusion must be discontinued. Administration of amiodarone** in unstable patients must be performed under continuous hemodynamic monitoring.

In patients with STEMI and rapid AF in the presence of acute heart failure (AHF) but absence of severe hypotension, intravenous amiodarone** is recommended for heart rate control [14, 401, 402].

ESC IC (LoE C, SoR 5)

Comments: If the QT interval increases > 500 ms, amiodarone** infusion must be discontinued. Administration of amiodarone** in unstable patients must be performed under continuous hemodynamic monitoring.

In patients with STEMI and AF in the absence of AHF and hemodynamic instability (severe hypotension), intravenous beta-blockers are recommended if necessary for heart rate control [14, 403].

ESC IC (RR S, ELD 5)

In patients with STEMI and new-onset AF during the acute phase of the disease, it is recommended to consider prescribing oral anticoagulants indefinitely, with a reassessment of overall antithrombotic therapy based on the risk of thromboembolic complications according to the CHA2DS2-VASc score and the bleeding risk according to the HAS-BLED score [14, 404-406].

ESC IIaC (LoE C, GoR 5)

Comment: The need to adjust the timing of dual antiplatelet therapy and single antiplatelet monotherapy as part of antithrombotic therapy in patients with STEMI and AF is determined by the balance of thromboembolic, ischemic, and hemorrhagic risks, and was previously discussed in the section "Antithrombotic therapy in other treatment strategies in patients with indications for long-term oral anticoagulation".

It is preferable to use direct oral anticoagulants (ATX groups: Direct thrombin inhibitors, B01AE, and Direct factor Xa inhibitors, B01AF), provided there are no contraindications.

3.4.2.3. Sinus bradycardia, atrioventricular block

In patients with STEMI who develop hemodynamically significant sinus bradycardia or hemodynamically significant AV block (with an inadequate escape rhythm), intravenous administration of positive chronotropic agents (epinephrine**, atropine**) is recommended to stabilize hemodynamics [14, 137, 407, 408].

ESC IC (RR S, ELD 5)

Comment: At a heart rate of < 40 bpm and/or pauses > 300 ms, atropine** 0.6–1.0 mg is administered. Epinephrine** belongs to the ATC group Adrenergic and dopaminergic agents, C01CA. If marked bradycardia persists, a pacemaker (PM)*** is implanted.

In patients with STEMI and hemodynamically significant sinus bradycardia or hemodynamically significant AV block (with an inadequate escape rhythm) where atropine** is ineffective, temporary endocardial pacing is recommended to stabilize the patient's condition, if physical and technical capabilities permit [14].

ESC IC (RR S, ELD 5)

In patients with STEMI who develop hemodynamically significant sinus bradycardia or hemodynamically significant AV block (with an inadequate escape rhythm) where prior revascularization was not performed or was incomplete, urgent coronary angiography with the intent to perform PCI (including complete revascularization) is recommended [14].

ESC IC (RR S, ELD 5)

In patients with STEMI who have general population indications for permanent pacemaker implantation, permanent pacemaker implantation is recommended no earlier than 5 days after STEMI onset [14, 409].

ESC IC (RR S, ELD 5)

Comment: The decision regarding permanent pacemaker*** implantation should be made on days 10–14 after STEMI onset. Earlier implantation (starting from day 5 of the disease) is appropriate in patients with hemodynamically significant bradycardia and late and/or incomplete revascularization in anterior STEMI, in the presence of bifascicular block, preexisting AV block before STEMI, or progression of AV block grade during the first day of the disease.

In patients with anterior STEMI, high-grade AV block, and severe heart failure, it is recommended to consider early initiation of cardiac resynchronization therapy, provided technical capabilities allow [14, 409].

ESC IIbC (Level of Evidence C, Grade of Recommendation 5)

Comment: The decision to initiate cardiac resynchronization therapy should be made taking into account the presence of intraventricular conduction delay in a patient with AV block, its severity, clinical severity of heart failure, and the degree of LV systolic dysfunction.

Cardiac pacing is not recommended in patients with STEMI and high-grade AV block if the AV block resolved after revascularization or spontaneously [409, 410, 411].

ESC IIIB (LoE C, GoR 5)

3.4.3. Mechanical complications

Mechanical complications of MI—free wall rupture, ventricular septal rupture, and acute mitral regurgitation due to ischemic damage to the valvular apparatus—are life-threatening conditions that occur in less than 1% of cases in the reperfusion era, more frequently in patients with STEMI.

The choice of the optimal management strategy for patients with mechanical complications of MI is carried out by a multidisciplinary heart team including a cardiologist, anesthesiologist, interventional cardiologist, and cardiovascular surgeon.

In patients with STEMI and mechanical complications presenting with hemodynamic instability, the use of an intra-aortic balloon pump (IABP) and/or other mechanical circulatory support devices is recommended as a temporary measure to stabilize the condition prior to surgical intervention [14, 412-415].

ESC IIaC (LoE C, GoR 5)

Left ventricular free wall rupture

In confirmed LV free wall rupture in a patient with STEMI presenting with cardiac tamponade or an increasing risk thereof, immediate pericardiocentesis followed by emergency surgical intervention is recommended [14, 413, 415, 523].

RSC IIaC (LoE C, GoR 5)

Ventricular septal rupture

In patients with STEMI presenting with ventricular septal rupture, surgical treatment (closure of the ventricular septal defect) is recommended to prevent mortality [14, 413, 414, 416].

RSC IIaC (LOC C, LOE 5)

Comment: The method and timing of the intervention depend on the nature of the defect and the patient's condition. In general, surgical VSR repair is preferred after stabilization; however, in the presence of severe hemodynamic impairment, emergency surgery is performed.

Acute mitral regurgitation

Acute mitral regurgitation typically develops on days 2–7 after STEMI onset due to papillary muscle or chordal rupture. The rupture may be complete or involve only individual muscle heads. Rupture of the posteromedial papillary muscle occurs most frequently due to its specific blood supply. In some cases, severe mitral regurgitation develops in patients with STEMI without papillary muscle rupture or infarction as a consequence of extensive LV damage with subsequent dilation and enlargement of the mitral annulus. Clinically, acute mitral regurgitation manifests as AHF, pulmonary edema, and occasionally cardiogenic shock. The diagnosis is confirmed by echocardiography.

In STEMI patients who develop acute mitral regurgitation, surgical treatment is recommended to resolve acute heart failure and prevent death — typically mitral valve replacement (mitral valve replacement under cardiopulmonary bypass; mitral valve annuloplasty under cardiopulmonary bypass; reconstruction of subvalvular mitral apparatus structures). The timing of the intervention depends on the severity of mitral regurgitation and the patient's condition. In most cases, emergency surgery is indicated [417-420].

ESC IIaC (LoE B, GoR 3)

Comment: The timing of the intervention depends on the degree of mitral regurgitation and the patient's condition. In most cases, the surgery is performed on an emergency basis.

In STEMI patients with acute mitral regurgitation, it is recommended to consider the use of an intra-aortic balloon pump (IABP) and/or other mechanical circulatory support devices as a temporary measure to stabilize the condition [14].

ESC IIbC (LoE C, GoR 5)

3.4.4. Pericarditis

Pericarditis may complicate the early period of STEMI (from several hours to 4 days) and usually resolves rapidly on its own (early post-infarction pericarditis, syn.: epistenocardic pericarditis) or develop later (in 1–2 weeks, symptoms sometimes lasting several weeks) – late post-infarction pericarditis, syn.: Dressler's syndrome. As a rule, the probability of pericarditis is directly dependent on the extent of myocardial infarction and has no independent prognostic significance. Classical Dressler's syndrome presenting as generalized polyserositis has recently become extremely rare.

Clinically, pericarditis manifests as widespread, poorly localized precordial pain; auscultation reveals a pericardial friction rub (heard in only one-third of patients, often for a short duration; it disappears if fluid accumulates in the pericardial cavity). ECG shows concordant ST-segment elevations, sometimes combined with PQ-segment depression. Pericarditis may be accompanied by a decrease in QRS voltage in all ECG leads. The detection of pericardial effusion, as well as monitoring changes in its volume, is performed using echocardiography.

In STEMI patients with early post-infarction pericarditis and pronounced clinical manifestations, the use of #ASA** at a dose of 500 mg every 8–12 hours is recommended as anti-inflammatory therapy [14, 421-423].

RSC IIaC (LOC C, LOE 5)

Comment: The duration of treatment usually does not exceed 5–7 days. The use of other non-steroidal anti-inflammatory drugs alternative to ASA** in post-infarction pericarditis is not justified due to the potential negative impact on the risk of cardiac events.

In STEMI patients with late post-infarction pericarditis and pronounced clinical manifestations, the use of #ASA** at a dose of 500–1000 mg every 6–8 hours (maximum daily dose 3000 mg) followed by a gradual taper of 250–500 mg every 2 weeks is recommended as anti-inflammatory therapy [14, 421].

RSC IIaC (LOC C, LOE 5)

As an adjunctive treatment for post-infarction pericarditis, #colchicine (autumn crocus seed extract) may be used for 3 months at a dose of 0.5 mg twice daily (in patients with body weight ≥ 70 kg) or 0.5 mg once daily (in patients with body weight < 70 kg) [421].

RSC IIaC (LOC C, LOE 5)

Acute left ventricular (LV) aneurysm typically develops in extensive anterior STEMI, especially in the absence of adequate reperfusion therapy. Acute LV aneurysm increases the likelihood of cardiac rupture, as well as complications such as heart failure, cardiac arrhythmias, pericarditis, LV mural thrombosis, and peripheral thromboembolism.

Virtually in at least half of all cases of extensive anterior STEMI, mural thrombosis in the LV cavity is detected. In the population of patients with extensive anterior STEMI, LV thrombosis occurs in more than 9% of cases. Echocardiography is the diagnostic method for acute LV aneurysm and LV cavity thrombosis.

In STEMI patients with a high clinical probability of LV thrombus but inconclusive echocardiographic results, cardiac MRI (contrast-enhanced cardiac magnetic resonance imaging) is recommended to confirm or exclude an LV thrombus, provided physical and technical capabilities are available [60, 61].

ESC IIaC (LoE B, GoR 2)

In patients with anterior STEMI and suboptimal visualization of an LV thrombus on routine transthoracic echocardiography, it is recommended to consider contrast echocardiography to confirm or exclude an LV thrombus, if physical and technical capabilities are available [51].

ESC IIbC (LoE C, GoR 4)

Comment: Contrast echocardiography is currently in the process of implementation into clinical practice in the Russian Federation.

In the presence of an LV thrombus in STEMI patients, the administration of oral anticoagulants (vitamin K antagonists or direct oral anticoagulants (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban)) for 3–6 months is recommended [424].

ESC IIaC (LoE C, GoR 5)

Comment: Absolute indications for prescribing anticoagulants include the following thrombus characteristics: a mobile (floating) free strand, large size (greater than 2–3 cm), marked protrusion into the LV cavity, structural heterogeneity, and thrombus fragmentation.

The traditional therapy for LV intracavitary thrombus is vitamin K antagonist therapy monitored by INR (target range 2.0–3.0); during the titration phase of the vitamin K antagonist, administration of a therapeutic dose of a parenteral anticoagulant should be continued. The use of DOACs is possible, but remains insufficiently studied.

Early post-infarction angina is a variant of unstable angina and requires urgent therapeutic measures. It can be caused by either re-thrombosis (partial or complete) of the infarct-related artery or stenosing lesions in other coronary arteries. Following PCI, the recurrence of anginal pain may be caused by stent thrombosis or coronary artery dissection. In the early period after MI, anginal pain may appear due to ischemia of viable myocardium in the peri-infarction zone (especially if reperfusion therapy was not performed) or, less commonly, in other vascular territories. Ischemia may be associated with another atherosclerotic plaque, sometimes located in a different coronary artery.

Early post-infarction angina should be differentiated from pain associated with pericarditis.

In the early period (up to 28 days inclusive) of STEMI, recurrent MI may develop, leading to an expansion of the injury zone. Recurrent MI should be ruled out in the event of a repeated anginal attack lasting more than 20 minutes, accompanied by elevated cardiac biomarkers, ECG changes, and the appearance of new regional wall motion abnormalities.

In STEMI patients who experience an anginal attack lasting more than 20 minutes, measurement of cardiac troponin I or T levels with a repeat assessment after 6 hours is recommended to diagnose recurrent MI. An increase in cardiac troponin levels by 20% or more from the baseline level, combined with criteria for myocardial ischemia, indicates recurrent MI [5, 14].

ESC IIaC (LoE C, GoR 5)

To prevent the expansion of the myocardial infarction zone in STEMI patients with early post-infarction angina and/or recurrent MI, coronary angiography and, if necessary, revascularization are recommended [14].

ESC IIaC (LoE C, GoR 5)

3.5. Right ventricular STEMI

Isolated right ventricular MI is rare, but concomitant right ventricular involvement in inferior STEMI is observed in at least 25% of patients. Clinically, right ventricular MI is characterized by arterial hypotension and jugular venous distension in the absence of signs of pulmonary congestion. Hypotension in right ventricular MI is associated with relative hypovolemia.

In patients with inferior STEMI, to rule out or detect right ventricular involvement in the necrosis zone, it is recommended to record an ECG in right precordial leads (ST-segment elevation ≥1 mm in leads V₃R and V₄R is a sign of right ventricular MI) and perform echocardiography to detect right ventricular regional wall motion abnormalities and right ventricular cavity dilation [14, 41, 425, 426].

ESC IIaC (LoE C, GoR 3)

Comment: Echocardiography allows for the detection of right ventricular regional wall motion abnormalities and cavity dilation.

In patients with STEMI involving the right ventricle, to eliminate hypotension it is recommended to ensure an increase in the volume of blood flowing to the right heart chambers by administering plasma expanders (e.g., sodium chloride** solution 0.9%). In a more severe situation, adrenergic and dopaminergic agents are recommended (ATC group Adrenergic and dopaminergic agents, C01CA) [14].

ESC IIaC (LoE C, GoR 5)

In STEMI involving the right ventricle, due to the risk of worsening relative hypovolemia, it is recommended to avoid diuretics and, particularly, peripheral vasodilators [14].

ESC IIIC (CGR C, LOR 5)

3.6. Treatment of elderly and senile patients

In elderly and senile patients with STEMI, it is recommended to use the same diagnostic and treatment strategies as in younger patients to improve their clinical status and prognosis [427, 428].

ESC IB (CGR B, LVE 2)

Comment: Impaired function of organs and organ systems may serve as a contraindication or limitation to a particular method, but age per se does not.

The anatomical complexity of coronary artery disease in elderly and senile patients, the presence of age-associated diseases and geriatric syndromes (frailty, falls, cognitive impairment, malnutrition, polypharmacy, decreased physical functioning, instrumental and basic functional activity, etc.) can reduce the efficacy of STEMI treatment and worsen the prognosis of such patients both during hospitalization and after discharge [429-432].

To improve the safety of antithrombotic agents and secondary prevention drugs in elderly and senile patients with STEMI, the choice and doses of these medications are recommended to be tailored taking into account renal filtration function, comorbidities, presence of geriatric syndromes (frailty, falls, cognitive impairment, polypharmacy, etc.), and specific contraindications to the medications [206, 427, 433, 434].

ESC IB (LoE A, GoR 2)

Comment: In elderly and senile patients with STEMI, it is advisable to assess the presence of geriatric syndromes and implement preventive measures during hospitalization to reduce the risk of delirium, malnutrition, and falls, as well as to plan discharge, outpatient follow-up, and rehabilitation measures taking into account functional status and the need for social assistance / long-term care system.

Ideally, the management of elderly and senile patients with STEMI should be carried out by a multidisciplinary team involving a geriatrician or cardiologist trained in geriatrics, starting from their stay in the intensive care unit [435-436].

Screening, prevention, and correction of geriatric syndromes in elderly and senile patients with STEMI are carried out in accordance with the principles set out in the clinical guidelines "Frailty", "Malnutrition in elderly and senile patients", and others depending on the identified geriatric syndromes [437, 438].

To increase treatment safety in every STEMI patient with frailty syndrome and significant comorbidities, an individualized approach to the choice and scope of interventional and pharmacological treatment is recommended with a thorough comprehensive assessment of all risks and benefits [427, 428, 439].

ESC IB (LoE A, GoR 1)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

All patients who have undergone STEMI are recommended to undergo cardiac rehabilitation (CR) to reduce the risk of death and hospitalization rate, improve prognosis, quality of life and psychosocial status, increase physical performance, restore cardiovascular system functions, promote healthy lifestyle, correct cardiovascular risk factors, and increase treatment adherence [440-444].

ESC IC (Level of Evidence A, Grade of Recommendation 1)

Comments: CR is represented by a three-stage system within which patient routing is carried out: Stage 1 - in structural units of a medical organization providing specialized, including high-tech, medical care in inpatient settings (intensive care unit (ICU) and cardiology department, vascular center ward or primary vascular center); Stage 2 - in an inpatient rehabilitation department; Stage 3 - in an outpatient setting [445].

The key components of a comprehensive CR program are: physical training (supervised, home-based), an educational program (information and training in the "School for ACS Survivors"), modification of major risk factors (smoking, unhealthy diet, dyslipidemia, hypertension, overweight / obesity, physical inactivity, hyperglycemia in diabetes mellitus), psychological support, and measures to improve patient adherence, combined with prescribed drug therapy in accordance with clinical guidelines.

The CR program should begin as early as possible after the patient's clinical condition stabilizes, be carried out on a scheduled basis, and be based on a patient-centered approach taking into account medical indications and contraindications to individual program components. All outpatients who have suffered an ACS and have not previously participated in CR programs are recommended to be referred for CR regardless of the time elapsed since the disease onset [445].

Exceptions are patients with a diagnosed condition of dementia.

The recommended total duration of the cardiac rehabilitation program across the three stages is at least 24 weeks. A longer duration of the CR program (at the outpatient stage) increases its efficacy.

In all patients after STEMI, the outpatient stage of CR is recommended to be conducted in person, remotely (at home using digital and mobile health tools), or in a blended format to increase patient coverage by rehabilitation and improve their adherence to CR and treatment in general [446-450].

ESC IIb B (CGR C, LVE 2)

To implement the CR program in patients after STEMI, it is recommended to form a multidisciplinary rehabilitation team at all stages to assess the patient's clinical and functional status, determine and conduct a set of rehabilitation measures [440, 445, 451-452].

ESC IA (CGR A, LVE 1)

Comments: The multidisciplinary rehabilitation team should include: a cardiologist, a physical and rehabilitation medicine physician, a physical rehabilitation specialist (exercise therapy instructor-methodologist), a medical psychologist and/or psychotherapist, a dietitian, a medical rehabilitation nurse (exercise therapy instructor), and other specialists upon request. To assess the patient's clinical status, level of functioning and vital activity, and the impact of personal and environmental factors, it is recommended to use standardized and valid diagnostic methods, as well as assessment tools based on the International Classification of Functioning, Disability and Health (ICF) [453, 454].

All patients after STEMI are recommended to undergo a graded exercise test (exercise test using a cycle ergometer or treadmill) or cardiopulmonary exercise testing (quantitative assessment of oxygen uptake under ergospirometry conditions — if available and with sufficient institutional experience), and if unavailable (or contraindicated) — a 6-minute walk test to assess functional status, exercise tolerance, select the optimal physical training regimen, and monitor their efficacy and safety [455, 456].

ESC IA (CGR C, LVE 5)

Comment: Exercise testing is performed before starting the physical training program and after completing the CR stage.

All patients who have undergone STEMI are recommended moderate-intensity aerobic physical training (exercise therapy using exercise equipment for heart and pericardial diseases; individual exercise therapy sessions for heart and pericardial diseases; group exercise therapy sessions for heart and pericardial diseases; biofeedback exercise therapy for heart and pericardial diseases) to improve functional status, reduce symptoms, increase physical performance, improve quality of life, reduce the risk of cardiovascular events, hospitalization rates, and mortality [440, 444, 452, 457-459].

ESC IC (Level of Evidence A, Grade of Recommendation 1)

Comment. In patients after STEMI, it is recommended to rule out contraindications to physical training before prescribing them (see Appendix A3. Main contraindications to physical training) [456, 460].

In the early stage 1 of CR, a stepwise expansion of physical activity and the use of physical exercise sets are recommended. At later stages (2 and 3), it is recommended to include physical training in the CR program in an individual format and/or in organized groups in a medical facility and/or at home after training [461].

The recommended duration of dynamic physical training (e.g., on a stationary bicycle or treadmill) is at least 30 minutes (total training session duration 45–60 minutes) with a frequency of at least 3 times a week (optimally 5–6 times a week); the intensity of the training load is moderate (55–69% of the maximum heart rate during exercise testing or in the zone of 12–14/20 points on the Borg scale; Borg Rating of Perceived Exertion, Borg RPE), and the training load level remains constant throughout the main phase of the workout [440, 458, 460, 462, 463].

For highly deconditioned patients and patients with heart failure, low-intensity interval training may be recommended at the start of the program.

To ensure the safety of physical rehabilitation, it is recommended to monitor the patient's condition (complaints, clinical symptoms, blood pressure, heart rate, and ECG levels) and assess the level of physical exertion using the Borg scale during training [463].

Patients with STEMI, upon completion of cardiac rehabilitation programs, are recommended to maintain physical activity at a moderate intensity of at least 150 minutes per week or high intensity of at least 75 minutes per week. If the patient is unable to maintain the recommended level of daily physical activity, this level should be within the patient's physical capabilities and correspond to their clinical status.

In selected patients with STEMI who have a low risk of complications (including atherothrombotic and ischemic risks) and upon their request, it is recommended to consider high-intensity interval training to increase physical performance and improve quality of life [464-466].

ESC IIb C (LoE A, GoR 1)

Comment: The prescription of high-intensity interval training should only be considered at stage 3 of cardiac rehabilitation in the absence of contraindications, after assessing all potential risks and the safety of this physical intervention.

Patients with STEMI are recommended to undergo an assessment of their psychosocial status using standardized questionnaires or clinical interviews to identify potential barriers to lifestyle modification and treatment adherence, individualize the cardiac rehabilitation program and increase its effectiveness, provide timely psychological support, improve quality of life, and reduce cardiovascular complications [467-469].

ESC IB (LoE C, GoR 5)

Comment: In the presence of clinically significant anxiety and/or depressive symptoms, psychological counseling and support are recommended, along with psychopharmacotherapy (as indicated), which, combined with structured education and physical training, can reduce depression symptoms, improve social functioning, cognitive profile, and the patient's quality of life [169, 170, 468, 470, 471].

All patients with STEMI are recommended to participate in an educational program in any available format (individually and/or in groups – "School for Patients with Acute Coronary Syndrome" in-person or online) to increase their awareness of the disease, its risk factors, and prevention; promote a healthy lifestyle, teach self-monitoring and self-care methods, and increase adherence to treatment and rehabilitation interventions [472, 473].

ESC IA (LoE C, GoR 5)

Comment: It is recommended to conduct at least 6–10 sessions; increasing the number of sessions enhances the effectiveness of the educational program (these sessions may be conducted in a remote support format).

5. Prevention and Dispensary Observation

5.1. Prevention

In addition to continuing medical therapy initiated in the early stages of STEMI treatment (Section 3.2), interventions for cardiovascular risk factor control and the prevention of sudden cardiac death are recommended (Section 3.3.2).

To reduce the risk of cardiovascular events among patients with STEMI, it is recommended to identify smokers and implement regular interventions aimed at complete smoking cessation, including the avoidance of passive smoking [474-476].

ESC IIaA (LoE A, GoE 1)

Comment: Smoking cessation measures should be initiated during the inpatient phase and continued after discharge. Behavioral and pharmacological interventions (nicotine replacement therapy, varenicline, or bupropion) are recommended.

To reduce the risk of adverse outcomes, patients with STEMI are recommended to adhere to healthy eating principles, maintain a normal body weight, engage in regular physical exercise, and limit alcohol intake [477-481].

ESC IB (Level of Evidence B, Grade of Recommendation 2)

Comment: Key characteristics of a healthy diet include: limiting the intake of saturated fats and trans-fatty acids to < 10% and < 1% of total daily caloric intake, respectively; sodium chloride to 5 g per day; readily digestible carbohydrates; consumption of large amounts of fruits (≥ 250 g per day), vegetables (≥ 250 g per day), and whole-grain products. Fish consumption is recommended 1–2 times a week (at least once a week for fatty fish), along with low-fat dairy products, lean meat and poultry, legumes, and unsalted nuts in the amount of 30 g per day.

Daily alcohol consumption should not exceed 1 standard drink for women and 1–2 standard drinks for men (1 standard drink equals 40 ml of spirits, 120 ml of dry wine, or 330 ml of beer).

The target body mass index values are 20–25 kg/m², and waist circumference should be less than 80 cm for women and less than 94 cm for men.

In patients with STEMI, blood pressure control and maintaining it at the target level are recommended to reduce the risk of ischemic events and death [281, 482-486].

ESC IA (LoE A, GoR 1)

Comment: The target blood pressure level in patients after STEMI is below 140/90 mm Hg. If well tolerated, lowering blood pressure to 130/80 mm Hg and below should be considered. Beta-blockers and ACE inhibitors are preferred for blood pressure control in patients after STEMI.

In patients with diabetes mellitus who have had a STEMI, it is recommended to provide treatment aimed at maintaining an individualized target glycated hemoglobin level chosen in conjunction with an endocrinologist (below 7.0% for most patients) to reduce the risk of micro- and macrovascular complications of diabetes [487,488].

ESC IIaB (LoE B, GoR 2)

Comment: In patients with type 2 diabetes mellitus, the use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors is promising, as they help reduce the frequency of cardiovascular complications in patients with atherosclerotic cardiovascular diseases.

Patients with STEMI are recommended to receive annual influenza vaccination to reduce the risk of cardiovascular complications and death [489-491].

ESC IA (LoE A, GoR 2)

In cases of inadequate risk factor control or the occurrence of cardiovascular complications during optimal medical therapy in patients with STEMI, it is recommended to consider the use of low doses (0.5 mg/day) of #Colchicum autumnale seed extract (colchicine) [492, 493].

ESC IIb A (LoE A, GoR 2)

In patients with STEMI, it is recommended to use fixed-dose drug combinations to increase treatment adherence and reduce the risk of adverse outcomes [494, 495].

ESC IIa B (LoE B, GoR 2)

5.2. Dispensary follow-up

Upon discharge from the hospital, a patient who has suffered a STEMI must be provided with information about their condition in both oral and written forms [496, 497].

ESC IIa B (LoE B, GoR 3)

It is recommended to establish dispensary follow-up (clinical monitoring) for all patients who have suffered a STEMI after their discharge from the hospital to implement a set of measures for the prevention and treatment of cardiovascular complications, timely adjustment of therapy, and improvement of treatment adherence [14, 504, 505].

ESC I C (LoE C, GoR 5)

It is recommended that dispensary follow-up for all patients in the first 12 months after STEMI be carried out by a cardiologist to implement a set of measures for the prevention and treatment of cardiovascular complications, timely adjustment of therapy, and improvement of treatment adherence. The minimum frequency of dispensary visits is 2 times a year; in cases of complicated disease progression, as well as when titration of medication doses is necessary (lipid-lowering drugs, beta-blockers, renin-angiotensin-aldosterone system blockers, vitamin K antagonists, etc.), the frequency of dispensary visits should be determined in accordance with clinical necessity [505].

ESC IC (LoE C, GoR 5)

Comments: In accordance with Order No. 168n of the Ministry of Health of the Russian Federation dated March 15, 2022, "On approval of the procedure for conducting dispensary follow-up for adults," dispensary monitoring of patients in the first 12 months after myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting is performed by a cardiologist.

In accordance with Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022, "On Approval of the Procedure for Dispensary Observation of Adults", after 12 months, lifelong dispensary observation is carried out by a general practitioner (family doctor); a consultation (examination, visit) by a cardiologist is carried out according to medical indications upon referral by the general practitioner (family doctor).

Continuation of dispensary observation by a cardiologist is prescribed in cases of effort angina FC III–IV, ineffectiveness of pharmacotherapy (refractory symptoms, failure to achieve target blood pressure, heart rate, LDL-C levels), presence of heart failure, life-threatening rhythm disorders, diabetes mellitus, CKD stage C4 and C5, combined antithrombotic therapy, symptomatic peripheral artery disease, or atherosclerosis of another vascular bed when prescribing dual antiplatelet therapy or combined antithrombotic therapy.

During visits, it is recommended to measure blood pressure and heart rate, determine body weight (calculating body mass index), measure waist circumference, and assess smoking status [505].

In patients after STEMI, to assess lipid metabolism disorders and control the effectiveness of lipid-lowering therapy, it is recommended to perform a biochemical blood test to assess lipid metabolism disorders (at least testing LDL-C levels) at least twice a year [505].

ESC IC (LoE C, GoR 5)

Comments: When selecting lipid-lowering therapy, LDL-C levels are recommended to be evaluated every 4–6 weeks until target values are reached (<1.4 mmol/L with at least a 50% reduction from baseline values).

In patients after STEMI, it is recommended to perform a complete blood count and general biochemical blood test (including eGFR calculation) at least once a year to monitor treatment safety and timely adjust therapy [505].

ESC IC (LoE C, GoR 5)

Comments: Complete blood counts and/or general biochemical blood tests may be performed more frequently according to clinical necessity.

When using direct oral anticoagulants, determination of CrCl is recommended.

In patients after STEMI taking vitamin K antagonists, it is recommended to determine INR at least twice a year to monitor treatment efficacy and safety, as well as to select the drug dose [505].

ESC IC (LoE C, GoR 5)

Comments: In most patients taking vitamin K antagonists, determining INR once a month is recommended; during the dose titration period or with fluctuating INR values, more frequent INR determinations may be necessary.

In patients after STEMI, it is recommended to perform an ECG at least once a year to detect signs of disease progression, cardiac rhythm and conduction disorders, and to timely adjust therapy [505].

ESC IC (LoE C, GoR 5)

Comments: An ECG may be recorded more frequently according to clinical necessity.

In patients after STEMI, it is recommended to perform chest X-ray at least once a year to detect signs of pulmonary congestion [505].

ESC IC (LoE C, GoR 5)

In patients after STEMI, it is recommended to perform echocardiography with mandatory assessment of LVEF at least once a year to monitor the dynamics of changes associated with previous ACS, detect new pathological changes, and timely adjust therapy [505].

ESC IC (LoE C, GoR 5)

Comments: Echocardiography may be performed more frequently according to clinical necessity.

In patients after STEMI who underwent PCI or CABG, it is recommended to perform a non-invasive stress test (see Terms and Definitions) at least once every 2 years to detect myocardial ischemia and/or assess its severity [505].

Comments: Non-invasive stress tests may be performed in all patients after STEMI according to clinical necessity.

ESC IC (LoE C, GoR 5)

6. Organization of Medical Care

6.1. Indications for hospitalization

Any suspicion of STEMI is an indication for emergency hospitalization.

Patients with STEMI should be hospitalized in regional vascular centers for patients with ACS, or in cardiology departments with intensive care units for patients with ACS (primary vascular centers). Since many patients with suspected ACS may require advanced differential diagnosis, it is optimal to hospitalize them in a multidisciplinary hospital with the capability for emergency diagnosis and treatment of acute coronary and other pathologies. Patient routing should be organized so that all patients are hospitalized or transferred as quickly as possible to a hospital with the capability for invasive treatment of ACS.

At the prehospital stage, instrumental/laboratory diagnostic procedures aimed at confirming or excluding the diagnosis of NSTE-ACS / STEMI are not recommended, with the exception of ECG [498-499].

ESC IC (RR S, ELD 5)

Comment: At the prehospital stage, registering an ECG is sufficient to make a decision on the further management of a patient with suspected STEMI. Determining the level of myocardial injury markers is impractical. If care is provided at the prehospital stage by a paramedic team, transmitting the ECG via communication channels to a specialized telemedicine center for cardiovascular risks is mandatory in order to coordinate patient management and routing.

If STEMI is suspected, a patient hospitalized in a facility lacking capabilities for emergency revascularization is recommended to be timely transferred to a medical institution where the ACS revascularization program is implemented [14].

ESC IC (RR S, ELD 5)

In each region, it is recommended to develop a regional patient routing protocol for NSTE-ACS / STEMI, taking into account current guidelines and regional characteristics [14].

ESC IC (RR S, ELD 5)

In each region, it is recommended to designate a specialized cardiosurgery department for emergency CABG surgery in patients with ACS, as well as to develop regional rules for the emergency transfer of such patients [14].

ESC IC (RR S, ELD 5)

6.2. Indications for patient discharge from the hospital

The duration of hospitalization is determined individually in accordance with the patient's cardiac risk, comorbidities, functional status, and social support. At the same time, patients should not stay in the hospital longer than necessary for psychosocial reasons and to prevent nosocomial infections.

After excluding the diagnosis of STEMI (e.g., after serial determination of blood troponin dynamics, possibly supplemented by other instrumental methods), the patient can be transferred to a specialized department (if there are indications for hospitalization) or discharged.

Patients are recommended to be discharged provided they are clinically stable, risk stratification for adverse outcomes is completed (including non-invasive stress tests in STEMI patients when indicated), and the chosen treatment strategy has been implemented.

The safety of early discharge (48–96 hours) after primary PCI is determined primarily by the absence of early complications, such as recurrent ischemia, stent thrombosis, acute heart failure, supraventricular and ventricular arrhythmias, conduction disorders, ventricular septal rupture or free wall rupture, acute mitral regurgitation, pericarditis, or left ventricular thrombus with the risk of systemic embolism.

Completed PCI and aggressive antithrombotic therapy can cause bleeding, both access-site related and other, primarily gastrointestinal and cerebral, as well as contrast-induced acute kidney injury. Recurrent MI in the postoperative period can be associated either with stent thrombosis or with critical stenosis or rupture of an unstable plaque in a non-culprit coronary artery segment.

The Zwolle score can be used as a risk stratification tool for early discharge, based on six clinical and angiographic features: patient age, Killip class of heart failure, MI location (anterior or other), time to reperfusion, presence of three-vessel disease, and TIMI flow in the infarct-related artery (Appendix G2). These factors have been shown to be independent predictors of 30-day mortality. Patients with ≤3 points on the Zwolle scale have a 0.5% risk of 30-day mortality and can be safely discharged from the hospital within the first 72 hours. The validity of the Zwolle score has been demonstrated in a number of studies [70, 71, 500-502].

Early discharge of low-risk STEMI patients after primary PCI is recommended in selected patients, provided that early rehabilitation and adequate follow-up are organized [502-503].

ESC IB (Level of Evidence A, Class of Recommendation 2)

Comment: In case of early discharge the patient should start rehabilitation during hospitalization, receive detailed information about the event, as well as about upcoming lifestyle modifications. In addition, pharmacotherapy as part of secondary prevention should be initiated (optimal antiplatelet therapy, beta-blocker, renin-angiotensin-aldosterone system blocker(s), HMG-CoA reductase inhibitor).

6.3. Other organizational technologies

In suspected STEMI, intensive monitoring in an intensive care unit (ward) with continuous electrocardiographic data monitoring (ECG monitoring) is recommended for heart rhythm control until the presence of STEMI is confirmed or ruled out, the risk of an adverse outcome is determined, the management strategy is chosen, and other life-threatening diseases and complications are excluded.

In uncomplicated STEMI in patients with no signs indicating an increased risk of life-threatening arrhythmias, intensive monitoring in an intensive care unit (ward) with continuous electrocardiographic data monitoring (ECG monitoring) for heart rhythm control is recommended for up to 24 hours or until successful PCI, if performed within the first 24 hours after hospitalization. In other cases, intensive monitoring with continuous electrocardiographic data monitoring (ECG monitoring) for heart rhythm control should be extended until clinical stabilization.

Continuous electrocardiographic data monitoring (ECG monitoring) for heart rhythm control should be extended beyond 24 hours if there is an increased risk of life-threatening arrhythmias (hemodynamic instability, prior serious arrhythmias, LVEF ≤ 40%, failed reperfusion attempts, persistent critical stenoses in major coronary arteries, complications during PCI). In patients without signs of ongoing myocardial ischemia, extension of continuous electrocardiographic data monitoring (ECG monitoring) for heart rhythm control is possible if coronary artery spasm is suspected, as well as in the presence of symptoms that do not allow arrhythmia to be ruled out.

Before discharge, all patients should undergo an assessment of long-term adverse event risk, taking into account LVEF, severity of coronary artery disease and completeness of coronary revascularization, presence of residual ischemia, complications noted during hospitalization, and levels of metabolic markers determined during the hospital stay: (blood total cholesterol, LDL-C, HDL-C, and triglyceride levels, fasting blood glucose levels, as well as renal filtration function parameters: blood creatinine level, with glomerular filtration rate calculation, and in case of prescribing direct oral anticoagulants, also creatinine clearance (CrCl).

7. Additional Information

Presented in Appendices A–B.

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care provided to adults with acute ST-segment elevation myocardial infarction (ICD-10 codes: I21.0, I21.1, I21.2, I21.3, I21.9, I22.0, I22.1, I22.8, I22.9, I24.0, I24.8, I24.9)

Item No.	Quality assessment criteria	Performance evaluation
1.	After discharge from the hospital, the patient was enrolled in dispensary follow-up	Yes/No
2.	A cardiac rehabilitation program is being implemented	Yes/No
3.	A general (clinical) blood count was performed at least once a year	Yes/No
4.	A general biochemical blood test (with eGFR calculation) was performed at least once a year	Yes/No
5.	A biochemical lipid profile blood test was performed (at least LDL-C testing) at least twice a year	Yes/No
6.	ECG recording was performed at least once a year	Yes/No
7.	Echocardiography with LVEF assessment was performed at least once a year	Yes/No
8.	Therapy with ASA in combination with a P2Y₁₂ platelet receptor inhibitor (clopidogrel, ticagrelor, or prasugrel), or oral anticoagulant therapy (apixaban, dabigatran etexilate, rivaroxaban, edoxaban, or a vitamin K antagonist) in combination with an antiplatelet agent (clopidogrel, less commonly ticagrelor) is administered depending on medical indications and in the absence of medical contraindications	Yes/No
9.	Therapy with high doses of HMG-CoA reductase inhibitor medications is administered in the absence of medical contraindications; if the target LDL-C level (<1.4 mmol/L) and a 50% reduction from baseline are not achieved, the dose of the HMG-CoA reductase inhibitor is increased or combination therapy is administered (with ezetimibe and/or another lipid-lowering agent (PCSK9 inhibitor)) depending on medical indications and in the absence of medical contraindications	Yes/No
10.	Therapy with ACE inhibitor or ARB medications is administered (at least in patients with LVEF ≤40%, heart failure, arterial hypertension, chronic kidney disease, diabetes mellitus) depending on medical indications and in the absence of medical contraindications	Yes/No
11.	Therapy with oral beta-blocker medications is administered (at least for LVEF ≤ 40%) in the absence of medical contraindications	Yes/No

Quality assessment criteria for specialized medical care provided to adults with acute ST-segment elevation myocardial infarction (ICD-10 codes: I21.0, I21.1, I21.2, I21.3, I21.9, I22.0, I22.1, I22.8, I22.9, I24.0, I24.8, I24.9)

N No.	Quality assessment criteria	Performance evaluation
1.	The medical documentation indicates the time interval from seeking medical care to the initiation of reperfusion treatment	Yes/No
2.	Administration of medications for thrombolytic therapy was performed no later than 10 minutes from diagnosis establishment (if primary PCI cannot be performed within 120 minutes from diagnosis to guidewire insertion into the infarct-related artery)	Yes/No
3.	Coronary angiography and, if necessary, PCI were performed within 2–24 hours after successful thrombolytic therapy	Yes/No
4.	The time from diagnosis establishment/confirmation in the PCI center to guidewire insertion into the infarct-related artery during primary PCI is less than 60 minutes	Yes/No
5.	Echocardiography with LVEF assessment was performed	Yes/No
6.	Blood troponin I or T testing was performed (at diagnosis establishment; if the first test is uninformative, repeated)	Yes/No
7.	Radial artery access was used for coronary angiography and PCI (in the absence of medical contraindications)	Yes/No
8.	Therapy with beta-blocker medications is administered (at least for LVEF ≤ 40%) in the absence of medical contraindications	Yes/No
9.	Therapy with ACE inhibitor or ARB medications is administered (at least in patients with LVEF ≤40%, heart failure, arterial hypertension, chronic kidney disease, diabetes mellitus) depending on medical indications and in the absence of medical contraindications	Yes/No
10.	Lipid-lowering therapy with high doses of HMG-CoA reductase inhibitor medications is administered in the absence of medical contraindications	Yes/No
11.	At the start of treatment, a combination of ASA, a P2Y₁₂ platelet receptor inhibitor (clopidogrel, ticagrelor, or prasugrel), and an anticoagulant was used, followed by a transition to a combination of ASA and a P2Y₁₂ platelet receptor inhibitor or, for patients with indications for long-term anticoagulant use, to a combination of an oral anticoagulant and an antiplatelet agent, depending on medical indications and in the absence of medical contraindications	Yes/No
12.	Before discharge from the hospital, the timeline for staged revascularization was determined (if indicated)	Yes/No

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Appendix A1. Working Group Composition

Steering Committee of the Working Group:

Averkov OV (Moscow)

Arutyunyan GK (Moscow)

Duplyakov DV (Samara)

Konstantinova EV (Moscow)

Nikulina NN (Ryazan)

Shakhnovich RM (Moscow)

Yavelov IS (Moscow)

Yakovlev AN (Saint Petersburg)

Other working group members:

Abugov SA (Moscow)

Alekyan BG (Moscow)

Aronov DM (Moscow)

Arkhipov MV (Yekaterinburg)

Barbarash OL (Kemerovo)

Boytsov SA (Moscow)

Bubnova MG (Moscow)

Vavilova TV (Saint Petersburg)

Vasilyeva EYu (Moscow)

Galyavich AS (Kazan)

Ganyukov VI (Kemerovo)

Gilyarevsky SR (Moscow)

Golubev EP (Moscow)

Golukhova EZ (Moscow)

Zateyshchikov DA (Moscow)

Karpov YuA (Moscow)

Kosmacheva ED (Krasnodar)

Lopatin YuM (Volgograd)

Markov VA (Tomsk)

Merkulov EV (Moscow)

Novikova NA (Moscow)

Panchenko EP (Moscow)

Pevzner DV (Moscow)

Pogosova NV (Moscow)

Prasol DM (Saint Petersburg)

Protopopov AV (Krasnoyarsk)

Skrypnik DV (Moscow)

Tarasov RS (Moscow)

Tereshchenko SN (Moscow)

Ustyugov SA (Krasnoyarsk)

Khripun AV (Rostov-on-Don)

Tsebrovskaya EA (Saint Petersburg)

Shalaev SV (Tyumen)

Shlyakhto E.V. (Saint Petersburg)

Shpektor A.V. (Moscow)

Yakushin S.S. (Ryazan)

The members of the Working Group confirmed the absence of financial support/conflict of interest. If a conflict of interest was reported, the working group member(s) were excluded from the discussion of sections related to the conflict of interest area.

Appendix A2. Methodology for Developing Clinical Guidelines

These guidelines are based on the results of major multicenter studies, meta-analyses, and registries, which also serve as the foundation for other national and international clinical guidelines. They incorporate the main provisions of the updated European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association guidelines for the diagnosis and management of ACS, the ESC guidelines on myocardial revascularization, the ESC guidelines on dual antiplatelet therapy, the ESC guidelines for the management of chronic coronary syndromes, as well as the relevant professional society guidelines on antithrombotic therapy in patients with AF. At the same time, differences and specific aspects of providing medical care to patients with ACS in the Russian Federation were taken into account.

Target audience for these clinical guidelines:

Cardiologist.
Anesthesiologist-Resuscitator.
Emergency Medical Technician / Feldsher.
Emergency Physician.
General practitioner / Physician.
General practitioner / district physician.
General practitioner (family physician).
Cardiovascular surgeon.
Endovascular Surgeon.

European Society of Cardiology (ESC) Class of Recommendation Scale

Since members of the Russian Society of Cardiology (RSC) are also members of the European Society of Cardiology (ESC), all ESC guidelines are developed with the participation of Russian experts who co-author the European guidelines. Thus, the existing ESC guidelines reflect the consensus of leading Russian and European cardiologists. Accordingly, the National Guidelines were formulated based on the ESC guidelines, taking into account national specifics, diagnostic and treatment features, and the availability of medical care. For this reason, the text of these clinical guidelines simultaneously employs two scales for assessing the level of evidence for recommendation statements: the ESC levels of evidence combined with the Russian reliability and validity levels (UUR and UDD). ESC classes of recommendations have been added to evaluate the necessity of performing recommendation statements (Tables 1, 2, 3, 4).

Table 1. Classes of Recommendations According to ESC Guidelines

ESC Class of Recommendation	Definition	Suggested Wording
I	Evidence and/or general agreement that a given diagnostic procedure, intervention/treatment is beneficial, useful, effective	Recommended / indicated
II IIa IIb	Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given procedure, intervention, treatment Weight of evidence/opinion is in favor of usefulness/efficacy Usefulness/efficacy is less well established by evidence/opinion	Should be considered apply May be considered apply
III	Data or consensus that a diagnostic procedure, intervention, or treatment is useless/ineffective, and in some cases may be harmful.	Not recommended apply

ESC Class of Recommendation

Definition

Suggested Wording

Evidence and/or general agreement that a given diagnostic procedure, intervention/treatment is beneficial, useful, effective

Recommended /

indicated

IIa

IIb

Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given procedure, intervention, treatment

Weight of evidence/opinion is in favor of usefulness/efficacy

Usefulness/efficacy is less well established by evidence/opinion

Should be considered

apply

May be considered

apply

III

Data or consensus that a diagnostic procedure, intervention, or treatment is useless/ineffective, and in some cases may be harmful.

Not

recommended

apply

Table 2. Levels of Evidence According to ESC Guidelines

Level ESC levels of evidence	Definition
A	Data derived from multiple randomized clinical trials or meta-analyses
B	Data derived from a single randomized clinical trial or large non-randomized studies
C	Consensus of expert opinion and/or results of small studies, retrospective studies, registries

Level

ESC levels of evidence

Definition

Data derived from multiple randomized clinical trials or meta-analyses

Data derived from a single randomized clinical trial or large non-randomized studies

Consensus of expert opinion and/or results of small studies, retrospective studies, registries

Table 3. Levels of Evidence (LE) grading scale for diagnostic methods (diagnostic interventions)

LoE	Definition
1	Systematic reviews of studies with reference standard control or systematic reviews of randomized clinical trials with meta-analysis
2	Individual studies with reference method control or individual randomized clinical trials and systematic reviews of studies of any design, excluding randomized clinical trials with meta-analysis
3	Studies without consecutive reference method control, or studies with a reference method that is not independent of the studied method, or non-randomized comparative studies, including cohort studies
4	Non-comparative studies, case report
5	Only justification of mechanism of action or expert opinion is available

Table 4. Levels of Evidence (LE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

LoE	Definition
1	Systematic review of RCTs incorporating meta-analysis
2	Individual RCTs and systematic reviews of studies of any design, excluding RCTs with meta-analysis
3	Non-randomized comparative studies, including cohort studies
4	Non-comparative studies, case reports or case series, case-control studies
5	Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available

Table 5. Grades of Recommendation (GR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

GoR	Definition
A	Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent)
B	Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent)
C	Weak recommendation (lack of evidence of appropriate quality; all considered efficacy criteria (outcomes) are unimportant, all studies have low methodological quality and their conclusions on the outcomes of interest are inconsistent)

Appendix A3. Reference Materials

Order of the Ministry of Health of the Russian Federation No. 918n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to Patients with Cardiovascular Diseases" (as amended on February 21, 2020).
Order of the Ministry of Health of the Russian Federation No. 612n dated June 10, 2021, "On Approval of the Standard of Medical Care for Adults with Acute ST-Segment Elevation Myocardial Infarction (Diagnosis, Treatment, and Dispensary Follow-up)."
Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022, "On Approval of the Procedure for Dispensary Monitoring of Adults."
"Methodological Recommendations for Assessing the Scientific Validity of Information Included in Clinical Guidelines" by the Center for Expertise and Quality Control of Medical Care of the Russian Ministry of Health, 2019.

Diagnostic Criteria for Myocardial Infarction

Diagnostic criteria for acute MI [5]

The term "acute MI" is used when there is evidence of acute myocardial injury (characteristic dynamics of blood biomarker levels) along with evidence of acute myocardial ischemia.

Diagnostic criteria for type 1 and type 2 acute MI

An increase and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit in patients without a baseline elevation of cardiac troponin, or a rise of >20% if the baseline values are elevated and are stable (variation ≤20%) or falling, combined with at least one of the following criteria for acute myocardial ischemia:

Symptoms of myocardial ischemia;
newly developed (или presumably newly developed) ischemic changes on the ECG;
appearance of pathological Q waves on the ECG;
imaging evidence of new areas of viable myocardium loss or regional wall motion abnormalities consistent with an ischemic etiology;
Detection of intracoronary thrombus by coronary angiography or atherothrombosis (or signs of unstable atherosclerotic plaque) at autopsy (for type 1 MI).

Criteria for the differential diagnosis of type 1 and type 2 MI are presented in Figure 3.

Diagnostic criteria for type 3 acute MI

Cardiac death in a patient with symptoms suggestive of myocardial ischemia, accompanied by presumed new ischemic ECG changes or ventricular fibrillation, occurring before blood samples can be obtained, before cardiac biomarker values rise in the blood, or confirmed at autopsy. If an autopsy reveals MI combined with fresh or recent atherothrombosis (or signs of unstable atherosclerotic plaque) in the culprit coronary artery, type 3 MI should be reclassified as type 1 MI.

Diagnostic criteria for type 4a acute MI (first 48 hours after PCI)

An increase in cardiac troponin concentration in the blood greater than 5 times the 99th percentile upper reference limit in patients with a normal baseline blood level (if the troponin concentration was elevated and stable (variation ≤20%) or falling prior to the procedure, it must rise by >20% after the procedure) combined with at least one sign of acute myocardial ischemia:

New ischemic ECG changes;
appearance of pathological Q waves on the ECG;
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology;
Angiographic findings consistent with a procedural limitation of coronary blood flow, such as coronary dissection, occlusion/thrombosis of a major epicardial artery or side branch, disruption of collateral flow, or distal embolization;
Post-mortem identification of a procedure-related thrombus in the target artery or an area of myocardial necrosis supplied by that artery.

Diagnostic criteria for type 4b acute MI

Criteria for type 1 acute MI combined with stent thrombosis documented by coronary angiography or autopsy.

Diagnostic criteria for type 4c acute MI

Criteria for type 1 acute MI where coronary angiography identifies restenosis as the sole cause of the MI (with no other potentially related lesions identified and no evidence of intracoronary thrombosis).

Diagnostic criteria for type 5 acute MI (first 48 hours after CABG)

An increase in cardiac troponin concentration in the blood greater than 10 times the 99th percentile upper reference limit in patients with a normal baseline blood level (if the troponin concentration was elevated and stable (variation ≤20%) or falling prior to the procedure, it must rise by >20% after the procedure) combined with at least one sign of acute myocardial ischemia:

appearance of pathological Q waves on the ECG;
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology;
Acute graft or native coronary artery occlusion documented by coronary angiography.

Biochemical diagnosis of acute MI should utilize cardiac troponin assays that ensure a coefficient of variation at the 99th percentile upper reference limit of no higher than 20% (optimally no higher than 10%).

Appendix A3. Reference materials — Acute ST-segment elevation myocardial infarction

Figure 2. Diagnosis and differential diagnosis of type 1 and type 2 acute myocardial infarction.

Diagnostic criteria for prior MI [5]:

Pathological Q waves on ECG (with or without preceding symptoms) in the absence of non-ischemic causes for pathological Q waves;
Imaging evidence of regions with loss of viable myocardium in a pattern consistent with an ischemic etiology;
Morphological findings characteristic of a healed MI.

Causes of elevated cardiac troponin levels in the blood

Myocardial injury (necrosis) due to acute myocardial ischemia - Atherosclerotic plaque ulceration/rupture with thrombosis
Myocardial injury (necrosis) due to acute myocardial ischemia driven by a supply/demand oxygen imbalance
Decreased myocardial perfusion: - Coronary artery spasm - Microvascular dysfunction - Coronary embolism - Coronary artery dissection - Sustained bradyarrhythmia - Hypotension or shock - Respiratory failure - Severe anemia	Increased myocardial oxygen demand: oxygen: - Sustained tachyarrhythmia - Severe hypertension with or without LV hypertrophy
Other causes of myocardial injury (necrosis)
Cardiac causes: - Heart failure - Myocarditis - Cardiomyopathy (any type) - Takotsubo syndrome - Myocardial revascularization procedures - Other cardiac interventions - Catheter ablation - Defibrillation - Cardiac contusion	Non-cardiac causes: - Sepsis, infectious disease - CKD - Stroke - Subarachnoid hemorrhage - PE, pulmonary hypertension - Infiltrative diseases - Chemotherapeutic agents - Critical conditions - Strenuous physical exertion

Myocardial injury (necrosis) due to acute myocardial ischemia

- Atherosclerotic plaque ulceration/rupture with thrombosis

Myocardial injury (necrosis) due to acute myocardial ischemia driven by a supply/demand oxygen imbalance

Decreased myocardial perfusion:

- Coronary artery spasm

- Microvascular dysfunction

- Coronary embolism

- Coronary artery dissection

- Sustained bradyarrhythmia

- Hypotension or shock

- Respiratory failure

- Severe anemia

Increased myocardial oxygen demand: oxygen:

- Sustained tachyarrhythmia

- Severe hypertension with or without LV hypertrophy

Other causes of myocardial injury (necrosis)

Cardiac causes:

- Heart failure

- Myocarditis

- Cardiomyopathy (any type)

- Takotsubo syndrome

- Myocardial revascularization procedures

- Other cardiac interventions

- Catheter ablation

- Defibrillation

- Cardiac contusion

Non-cardiac causes:

- Sepsis, infectious disease

- CKD

- Stroke

- Subarachnoid hemorrhage

- PE, pulmonary hypertension

- Infiltrative diseases

- Chemotherapeutic agents

- Critical conditions

- Strenuous physical exertion

Diseases and conditions complicating ECG diagnosis of STEMI

Early cardiac repolarization syndrome
LBBB
Ventricular pre-excitation via an accessory pathway
LV hypertrophy
Brugada syndrome
Pericarditis, myocarditis
Pulmonary embolism
Subarachnoid haemorrhage
Metabolic disorders (e.g., hyperkalemia)
Cardiomyopathy
Cholecystitis
Persistent ECG changes characteristic of young age
Incorrect electrode placement
Prior MI with pathological Q waves and/or persistent ST elevation (e.g., chronic LV aneurysm)
Ventricular paced heart rhythm

Thrombolytics and their dosing regimens in STEMI^&

Alteplase**	a) 90-minute (accelerated) dosing regimen for STEMI patients in whom treatment can be initiated within 6 hours of symptom onset: 15 mg IV bolus, 50 mg IV infusion over the first 30 minutes, followed by a 35 mg infusion over 60 minutes up to a maximum dose of 100 mg. In patients with a body weight of less than 65 kg, the total dose is adjusted for weight: 15 mg IV bolus, 0.75 mg/kg (maximum 50 mg) via IV drip over 30 minutes, followed by an infusion of 0.5 mg/kg (maximum 35 mg) over 60 minutes. b) 3-hour dosing regimen for patients in whom treatment can be initiated between 6 and 12 hours after symptom onset: 10 mg IV bolus; 50 mg IV infusion over the 1st hour, followed by an IV infusion at a rate of 10 mg over 30 minutes, up to a maximum dose of 100 mg over 3 hours. In patients with a body weight of less than 65 kg, the total dose should not exceed 1.5 mg/kg.
Prourokinase**	Patient body weight >85 kg: IV bolus of 2,000,000 IU followed by infusion of 6,000,000 IU over 60 minutes. Patient body weight 60–85 kg: IV bolus of 2,000,000 IU followed by infusion of 4,000,000 IU over 60 minutes. Patient body weight <60 kg: IV bolus of 2,000,000 IU followed by infusion of 100,000 IU/kg × [body weight in kg] minus 2,000,000 IU over 60 minutes.
Recombinant protein containing the amino acid sequence of staphylokinase**	1. Single intravenous bolus injection at a dose of 15 mg (preferred for pre-hospital administration); 2. First intravenous bolus of 10 mg, repeat bolus of 5 mg 30 minutes after the first; 3. Intravenous bolus of 10 mg, followed by intravenous infusion of 5 mg over 30 minutes.
Streptokinase	IV infusion of 1,500,000 IU over 60 minutes
Tenecteplase**	Single IV bolus (administered over up to 5 seconds, depending on patient body weight). The recommended total dose should not exceed 50 mg: 30 mg for body weight <60 kg, 35 mg for body weight 60 to <70 kg, 40 mg for body weight 70 to <80 kg, 45 mg for body weight 80 to <90 kg, 50 mg for body weight ≥90 kg.

Notes: ^& — represents agents available and approved for use in the Russian Federation. All thrombolytics listed in the table, except streptokinase, are considered fibrin-specific.

Antithrombotic agents in STEMI

Drug	Recommendations for use
Antiplatelet agents (ATC group: Platelet aggregation inhibitors excluding heparin, B01AC)
#ASA** [14]	Oral; initial dose #150–300 mg (chewed and swallowed), from day 2 onwards — #75–100 mg once daily
#Clopidogrel**	Primary PCI support: oral; initial dose 600 mg [14], then 75 mg once daily. Thrombolytic therapy (TLT) support: oral; initial dose 300 mg or 75 mg in patients over 75 years of age; from day 2, 75 mg once daily. PCI support shortly after TLT: within the first 24 hours of thrombolytic administration in patients who have not received a loading dose of clopidogrel, give 300 mg; after 24 hours of thrombolytic administration in patients who have not received a loading dose of clopidogrel, give 600 mg; in those who received a loading dose of 300 mg on the first day, give an additional 300 mg. No reperfusion therapy: oral 75 mg once daily; prior to PCI at a later stage of the disease — loading dose of #600 mg [14].
Prasugrel	Primary PCI support: oral; 60 mg, from the following day 10 mg once daily (in patients aged ≥ 75 years or with a body weight < 60 kg, 5 mg once daily).
Ticagrelor**	Primary PCI support: oral; initial dose 180 mg, followed by 90 mg twice daily 12 hours later (can be used in patients who received a loading dose of clopidogrel**). When extending treatment 1 year after STEMI in patients at high risk for ischemic events, 60 mg twice daily.
Platelet GPIIb/IIIa receptor blockers (used as PCI support)
Abciximab	IV; 0.25 mg/kg over 3–5 min.
Tirofiban	IV; initial dose 25 µg/kg as a bolus injection over 3 min, followed by an infusion at a rate of 0.15 µg/kg/min for 12–24 h (minimum duration 12 h) and up to 48 h [14].
Eptifibatide	IV bolus of 180 µg/kg, followed by continuous infusion at 2 µg/kg/min (if serum creatinine is below 1.912 mmol/L) or 1 µg/kg/min (if serum creatinine is 1.912–3.824 mmol/L). 10 minutes after starting the infusion, repeat the bolus of 180 µg/kg. The infusion is continued for 18–24 h or until hospital discharge, if earlier, but for at least 12 h.
Parenteral anticoagulants
Unfractionated Heparin (unfractionated heparin**)	During PCI: UFH (unfractionated heparin) is administered intravenously as a bolus at a dose of 70–100 IU/kg (if GPIIb/IIIa receptor inhibitors are not planned) or at 50–60 IU/kg (when used concomitantly with GPIIb/IIIa receptor inhibitors). If necessary, repeat boluses to maintain the blood ACT at 250–350 s (200–250 s when using platelet GPIIb/IIIa inhibitors). TLT support: IV; bolus of 60 IU/kg (maximum 4000 IU) immediately followed by continuous infusion at 12 IU/kg/h (maximum 1000 IU/h), with subsequent dose adjustment to maintain aPTT at 50–70 seconds or 1.5–2 times the upper limit of the laboratory's control value (upper limit of normal or mean normal value in healthy individuals); when combined with TLT, aPTT should be measured at 3, 6, 12, and 24 hours after starting UFH** infusion; infusion duration is 24–48 hours. Without reperfusion therapy, including other indications for therapeutic anticoagulant doses: IV, bolus of 60–70 IU/kg (maximum 5000 IU), immediately followed by an infusion at an initial rate of 12–15 IU/kg/h (maximum 1000 IU/h); subsequently, dose titration to maintain aPTT at 1.5–2.5 times the control value for the specific laboratory (upper limit of normal or mean normal value in healthy individuals).
Bivalirudin	Primary PCI support: IV bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h during the procedure (if necessary, the infusion can be continued at the same dose for 4 h, and then at 0.25 mg/kg/h for up to 12 h); in patients with reduced creatinine clearance, the infusion rate should be reduced in accordance with the product labeling. In patients with a creatinine clearance of 30–59 mL/min, the bolus size remains unchanged, but the infusion rate should be reduced to 1.4 mg/kg/h; in patients with creatinine clearance < 30 mL/min or those on dialysis, bivalirudin is contraindicated.
#Enoxaparin sodium**	TLT support (in men with blood creatinine < 2.5 mg/dL [221 µmol/L] and women with blood creatinine < 2.0 mg/dL [177 µmol/L]): IV bolus of 30 mg; 15 minutes later, subcutaneous abdominal injection at a dose of 1 mg/kg twice daily up to day 8 of illness, hospital discharge, or successful PCI, whichever comes first (the first two subcutaneous doses must not exceed 100 mg). In individuals ≥ 75 years, the initial IV dose is not administered, and the maintenance dose is reduced to 0.75 mg/kg (the first 2 doses must not exceed 75 mg). In renal impairment (creatinine clearance < 30 mL/min), the drug is administered subcutaneously at 1 mg/kg once daily regardless of age. Primary PCI support: IV bolus of 0.5 mg/kg; if the procedure lasts longer than 2 hours, an additional bolus of 0.25 mg/kg [524, 525]. This dose is also used in patients taking direct oral anticoagulants (ATC groups: Direct thrombin inhibitors, B01AE, and Direct factor Xa inhibitors, B01AF). PCI against the background of initiated therapeutic doses of enoxaparin sodium: if no more than 8 hours have passed since the subcutaneous injection, no additional anticoagulants are required (if only a single subcutaneous injection of enoxaparin sodium was given, administer 0.3 mg/kg IV bolus before the procedure [14, 193, 526]); after 12 hours from the last injection, any anticoagulant can be used during PCI (including enoxaparin sodium as an IV bolus at 0.5 mg/kg). The catheter sheath may be removed from the femoral artery 6–8 hours after the last subcutaneous injection of enoxaparin sodium and 4 hours after IV administration. Prevention of venous thrombosis and PE: subcutaneous abdominal injection, 40 mg once daily (unless higher anticoagulant doses are required).
Sodium fondaparinux	Support for streptokinase TLT or absence of reperfusion therapy (in patients with blood creatinine < 3.0 mg/dL or 265 µmol/L): IV bolus of 2.5 mg; from day 2, subcutaneous abdominal injection at 2.5 mg once daily up to day 8 of illness, hospital discharge, or successful PCI, whichever comes first. Contraindicated at creatinine clearance < 20 mL/min. Prevention of venous thrombosis and PE: subcutaneous abdominal injection 2.5 mg once daily (unless higher anticoagulant doses are required).

Antithrombotic drug doses in renal impairment [14]

Drug		eGFR 30–59 mL/min/1.73 m² or CrCl 30–59 mL/min	eGFR 15–29 mL/min/1.73 m² or CrCl 15–29 mL/min		eGFR < 15 mL/min/1.73 m² or CrCl < 15 mL/min
Antiplatelet agents
ASA**	Emergency care	Dose unchanged
ASA**	Scheduled prescription	According to the instructions, ASA** is contraindicated in severe renal impairment without specifying CrCl/eGFR values. In such cases, an individual benefit/risk assessment of the prescription is recommended.
Clopido- grel**¹	Emergen- cy care	Usual dose	Usual dose	No data. In such cases, an individual benefit/risk assessment is recommended taking into account the product labeling².
Clopido- grel**¹	Scheduled prescription	Usual dose	Usual dose
Prasugrel		Usual dose	Usual dose	The experience with prasugrel in patients with renal impairment is limited. No dose adjustment is required for patients with renal impairment, including end-stage renal disease. However, ESC Guidelines do not recommend its use [14].
Ticagrelor**³		Usual dose	Usual dose	There is no information on the use of the drug in patients on hemodialysis, therefore its use in these patients is not indicated. Dose adjustment is not required in patients with renal impairment. However, ESC Guidelines do not recommend its use.
FRaMon monoclonal antibody Fab fragments		There are no renal function restrictions in the product labeling. Consideration of the overall bleeding risk is recommended.
Tirofiban		There are no renal function restrictions in the product labeling. Consideration of the overall bleeding risk is recommended.
Eptifibatide1		CrCl ≥ 50 mL/min: usual dose. CrCl ≥ 30 but < 50 mL/min: infusion dose reduced to 1.0 µg/kg/min.	No data. ESC clinical guidelines do not recommend use.
Anticoagulants
Heparin sodium** (UFH)		Dose is titrated under aPTT monitoring regardless of renal filtration function
Enoxaparin sodium**		Usual dose	According to the instructions, in severe renal impairment (without specifying quantitative level): in patients <75 years: increase the dosing interval from 12 to 24 h; in patients ≥75 years and older: increase the dosing interval from 12 to 24 h, with a dose of 1 mg/kg per administration.		Not recommended (no data)
Fondaparinux sodium1		Not recommended in patients with CrCl <20 mL/min. Dose adjustment is not required in patients with CrCl ≥20 mL/min.
Bivalirudin		Dose remains unchanged, except for patients scheduled for PCI: the infusion rate should be reduced to 1.4 mg/kg/h (the initial bolus dose of 0.75 mg/kg remains unchanged). During PCI, it is recommended to monitor clotting time, e.g., ACT. The ACT value should be checked 5 min after the initial bolus injection. If the ACT value is less than 225 s, a repeat bolus of 0.3 mg/kg should be administered and the ACT checked again 5 min after the repeat dose.	Contraindicated
Rivaroxaban**1 at a dose of 2.5 mg twice daily		Dose unchanged, but use with caution when co-administered with drugs that increase plasma concentrations of rivaroxaban**.	Dose unchanged, but use with caution		Contraindicated (no data)

Notes: CrCl — creatinine clearance;

¹ - for these drugs, according to the instructions, renal function assessment for safety of administration should be performed using CrCl;

² - after repeated doses of clopidogrel** at 75 mg/day in patients with severe renal impairment (CrCl — 5 to 15 mL/min), inhibition of ADP-induced platelet aggregation (25%) was lower compared to healthy volunteers, but the prolongation of bleeding time was comparable to that in healthy volunteers receiving clopidogrel** at 75 mg/day.

³- As a preventive measure, the use of ticagrelor should be avoided in patients with hyperuricemic nephropathy.

Medical treatment of STEMI

Table 1

β-Adrenergic receptor blockers in STEMI

Drug	Dose*
Parenteral forms
Metoprolol**	IV slowly under ECG and BP monitoring, 5 mg 2–3 times at intervals of at least 2 min; if well tolerated, 15 min after the last IV administration, switch to oral intake up to 50 mg every 6 h for 48 h.
Esmolol	In supraventricular tachycardia (except for ventricular pre-excitation syndrome) when other IV or oral beta-blockers are inappropriate or impossible to use, IV infusion under ECG and BP monitoring; loading dose 0.5 mg/kg over 1 min, then 0.05 mg/kg/min for 4 min, with insufficient effect, increase infusion rate by 0.05 mg/kg/min every 4 min up to 0.3 mg/kg/min; if a more rapid effect is needed, additional boluses of 0.5 mg/kg can be administered before the 2nd and 3rd dose increases. The hemodynamic effect persists for 20–30 min after stopping the infusion. When switching to other oral beta-blockers 1 hr after their first administration, the esmolol dose should be reduced by 50%; esmolol is usually discontinued after the oral administration of the second beta-blocker dose, provided that adequate heart rate and BP have been maintained during this time.
*Oral forms^, ^&**
#Carvedilol** ^#	Oral; initial dose 3.125–6.25 mg twice daily, if well tolerated, increase the dose at intervals of 3–10 days up to 25 mg twice daily. In patients with CHF and other contraindications to beta-blockers, slow dose titration is appropriate.
Metoprolol**	The target oral dose of metoprolol in MI is 100 mg twice daily, or 200 mg once daily for prolonged-release forms. Initial dose 12.5–25 mg twice daily in patients with CHF and other limitations to beta-blocker use.

Notes: Within the same group, drugs are listed alphabetically; treatment with β-blockers initiated in the first 24 hours of the disease in the absence of contraindications should be continued indefinitely;

*approximate doses are indicated, which may be lower or somewhat higher depending on individual tolerance and clinical effect in a particular patient;

**other drugs in appropriate doses without intrinsic sympathomimetic activity may also be used;

^#evidence of a positive effect on survival was obtained in patients with significantly impaired LV contractility (EF ≤40%);

^&a positive effect on survival in CHF patients with significantly impaired LV contractility has been demonstrated for bisoprolol** at a target dose of 10 mg once daily, carvedilol** at a target dose of 25 mg twice daily, and prolonged-release metoprolol succinate at a target dose of 200 mg once daily.

Table 2

Renin-angiotensin-aldosterone system blockers in STEMI

Drug	Dose*
Angiotensin-converting enzyme inhibitors
Captopril**	Oral; first dose 6.25 mg, 12.5 mg after 2 hours, 25 mg after 12 hours. Target dose 100 mg in 2 divided doses for 4 weeks. After 4 weeks, the patient's condition should be reassessed and, if well tolerated, therapy continued at a dose of 50 mg 3 times a day.
Lisinopril**	Oral; first dose 5 mg, after 24 h – 5 mg; target dose 10 mg once daily.
Zofenopril	Oral; 7.5 mg twice daily on days 1–2, if well tolerated 15 mg twice daily on days 3–4, then 30 mg twice daily.
Ramipril** ^&	Oral; initial dose: 2.5 mg once daily. It is recommended to double the dose at intervals of 1–2 weeks; target dose 5 mg twice daily
Enalapril**	Oral; initial dose 2.5 mg; target dose 10 mg twice daily.
Angiotensin II receptor blockers
Valsartan	Oral; first dose 20 mg twice daily with gradual titration up to 160 mg twice daily.
Aldosterone antagonists
Eplerenone^#	Oral when blood creatinine is <2.5 mg/dL (220 µmol/L) in men, <2.0 mg/dL (177 µmol/L) in women, and blood potassium is <5 mmol/L; first dose 25 mg once daily, if well tolerated in patients not taking amiodarone**, diltiazem, or verapamil, increase the dose to 50 mg once daily over the next 4 weeks.
#Spironolactone**	When indicated (see section 3.2.7.), orally when blood creatinine is < 220 µmol/L and blood potassium is <5 mmol/L; dose - 25 mg once daily. Withhold when blood potassium is >5.5 mmol/L, discontinue when blood potassium is > 6 mmol/L [300, 535, 536].

Notes: Within the same group, drugs are listed alphabetically; ACE inhibitor therapy should be started as early as possible (from the first hours of the disease) as soon as hemodynamics stabilize (specifically, SBP becomes not <100 mmHg) and continued indefinitely in the absence of contraindications;

*features of dose titration in a particular patient depend on the BP response, blood creatinine and potassium levels; if the target dose of the drug cannot be achieved, the maximally tolerated dose should be used.

Table 3

Organic nitrates

Drug	Dose
Nitroglycerin**	Intravenous infusion 5–166 µg/min; usually starting with an infusion of 10–20 µg/min with a possible increase by 5–10 µg/min every 5–10 min until symptoms decrease and/or systolic BP decreases by 10–15% with initially normal BP, and by 25–30% with hypertension (but not lower than 95 mmHg).

Intravenous insulin therapy in STEMI

Indications for insulin therapy in patients with STEMI and diabetes

Type 1 diabetes mellitus
Plasma glucose upon admission and subsequent measurements persistently above 10 mmol/L
Diabetic ketoacidosis
Hyperosmolar hyperglycemic state
Known high-dose steroid treatment
Parenteral nutrition
Severe/critical condition
Cardiogenic shock, pronounced congestive heart failure, severe post-infarction angina, arterial hypotension, severe cardiac arrhythmias
Any degree of impaired consciousness

Algorithm for continuous intravenous insulin infusion

Continuous intravenous insulin infusion is performed via a separate syringe pump using a solution of rapid-acting insulins and analogs at a concentration of 1 IU/1 ml of 0.9% sodium chloride solution**. In the absence of a syringe pump, intravenous drip administration is permitted.
It is recommended to determine plasma glucose levels once an hour until stabilization within the chosen target range for at least 4 hours; then once every 2 hours for 4 hours; thereafter, once every 4 hours. In critically ill patients, plasma glucose must be determined hourly even at a stable target level.
The recommended average starting rate of continuous intravenous insulin infusion in patients already within the target plasma glucose range is 0.5–1 IU/h; for those outside the target range, 2–3 IU/h (in the presence of ketoacidosis, 0.1 IU/kg body weight per hour, but not exceeding 15 IU/h). A lower starting rate (<0.5 IU/h) is used in underweight patients, renal, hepatic, or adrenal insufficiency. A higher starting rate (>3 IU/h) is used in ultra-high hyperglycemia (over 25 mmol/L) and suspected insulin resistance (pronounced obesity, signs of infection, chronic steroid therapy).
Simultaneously with continuous intravenous insulin infusion, it is advisable to establish an infusion of a 5–10% glucose solution (administering 5 g of glucose per hour is required). It is important to administer insulins and dextrose** via separate infusion sets, as frequent separate adjustments of the infusion rate for each of the two solutions are required. When plasma glucose levels are above 14 mmol/L, glucose is not administered (until the next glucose level determination).
If plasma glucose is less than 3.3 mmol/L, insulin infusion must be stopped and 30–60 ml of 40% glucose solution administered intravenously; repeat dextrose** administration every 20 minutes if necessary. After double confirmation of plasma glucose levels above 3.9 mmol/L, insulin infusion should be resumed at a lower rate.
When switching to subcutaneous insulin administration, the infusion is stopped 1–2 hours after the first subcutaneous injection of rapid-acting insulins and analogs, or 2–3 hours after the first injection of long-acting insulins and analogs.

Recommended insulin infusion rate depending on plasma glucose levels

Glucose (mmol/L)	<3,9	3,9–6,1	6,2–6,6	6,7–8,3	8,4–9,9	10–13,3	13,4–16,6	16,7–19,9	>20
Insulin administration rate (IU/h)	Do not administer	0,2	0,5	1	1,5	2	3	4	6

Selected patients (those previously receiving over 80 IU of insulin per day, receiving corticosteroids, or not achieving target glycemia using the proposed algorithm) may require more intensive algorithms. Patients with repeated plasma glucose measurements below 3.9 mmol/L (twice in a row) must be switched to a less intensive algorithm. These algorithms can be found in the guidelines for the management of patients with diabetes mellitus.

Classification of heart failure in MI according to Killip [358, 359]

Class	Features	In-hospital mortality*
I	No signs of heart failure	2–3%
II	S3 gallop, rales in the lower lung fields	5–12%
III	Pulmonary edema, rales above the scapular angles	10–20%
IV	Cardiogenic shock	50–81%

Hemodynamic variants of cardiogenic shock

Volumic status
	Wet	Dry
Cold	Classic cardiogenic shock (↓CI, ↑SVR, ↑PCWP)	Euvolemic cardiogenic shock (↓CI, ↑SVR, normal PCWP)
Warm	Vasodilatory cardiogenic shock or mixed shock (↓CI, ↓SVR, ↑PCWP)	Vasodilatory (non-cardiogenic) shock (↑CI, ↓SVR, ↓PCWP)

Volumic status

Wet

Dry

Cold

Classic

cardiogenic shock

(↓CI, ↑SVR, ↑PCWP)

Euvolemic cardiogenic shock

(↓CI, ↑SVR, normal PCWP)

Warm

Vasodilatory cardiogenic shock or mixed shock

(↓CI, ↓SVR, ↑PCWP)

Vasodilatory

(non-cardiogenic) shock

(↑CI, ↓SVR, ↓PCWP)

Notes: PCWP – pulmonary capillary wedge pressure, SVR – systemic vascular resistance, CI – cardiac index, ↓ – decrease, ↑ – increase.

Parameters to monitor in a patient with cardiogenic shock

Parameter	Nomenclature of medical services	Measurement frequency	Rationale
Cardiomonitoring, pulse oximetry, respiratory rate	A12.30.004 24-hour bedside monitoring of vital functions and parameters, A05.10.007 Electrocardiographic monitoring, A05.12.008 Percutaneous monitoring of partial oxygen pressure, A02.12.001.001 Pulse monitoring examination, B03.003.003 24-hour observation by an anesthesiologist- reanimatologist, B03.003.005 24-hour observation of an intensive care patient B03.015.002 Monitoring the degree of myocardial damage in myocardial infarction	Continuously	High percentage of arrhythmias, high risk of pulmonary edema, mechanical ventilation
Invasive blood pressure measurement (arterial line)	A11.12.012 Catheterization of extremity arteries, A02.12.002.002 Remote monitoring of blood pressure indicators, A14.12.001 Vascular catheter care	Continuously	Discontinuation of invasive blood pressure monitoring no earlier than 12–24 hours after stopping vasoactive drugs
CVP	A02.12.003 Central venous pressure measurement, A11.12.001 Catheterization of subclavian and other central veins, A14.12.001 Vascular catheter care	At least 4 times a day	Continuous CVP monitoring allows assessment of the patient's volume status
Mixed venous oxygen saturation	A11.12.001 Catheterization of subclavian and other central veins B03.016.011 Blood gas and acid-base balance analysis A14.12.001 Vascular catheter care B03.003.003 24-hour observation by an anesthesiologist- intensivist	Every 4 h	Monitoring mixed venous saturation allows for assessing changes in cardiac output and the effectiveness of vasoactive therapy
Urine output rate	A11.28.007 Urinary bladder catheterization, B03.003.005 24-hour observation of an intensive care patient, A14.28.002 Urinary catheter care	Every hour	Urine output rate and serum creatinine level are indicators of renal perfusion
Invasive hemodynamic monitoring and non-invasive cardiac output monitoring	A11.12.001 Catheterization of subclavian and other central veins, A11.10.005 Cardiac chamber catheterization, A24.12.001 Hemodynamic study by thermodilution, A04.10.002 Echocardiography, A12.10.003 Cardiac output study, A14.12.001 Vascular catheter care	As needed	Mandatory when initial therapy is ineffective and the diagnosis is unclear
Complete blood count (CBC)	B03.016.002 Complete blood count B03.016.003 Expanded complete blood count	Every 12–24 h	More frequently for patients with potential bleeding
Electrolytes	A09.05.031 Blood potassium level testing, A09.05.127 Serum total magnesium level testing, A09.05.034 Blood chloride level testing, A09.05.030 Blood sodium level testing, A09.05.032 Blood total calcium level testing	Every 6–12 h
Creatinine	A09.05.020 Blood creatinine level testing	Every 12–24 h
AST, ALT, LDH, bilirubin	A09.05.041 Blood aspartate aminotransferase activity assay, A09.05.042 Blood alanine aminotransferase activity assay, A09.05.039 Blood lactate dehydrogenase activity assay, A09.05.021 Blood total bilirubin level testing	Daily	Monitoring of hepatic congestion and acute liver injury
Lactate	B03.016.011 Acid-base balance and blood gas analysis	Every 1–4 h	Lactate clearance reflects the severity of multiple organ dysfunction syndrome. Decreased lactate clearance is associated with increased mortality
Coagulogram (exploratory hemostasis study)	B03.005.006 Coagulogram (exploratory hemostasis study)	Every 4–6 h for patients receiving continuous UFH** infusion, every 24 h for patients without anticoagulants

Notes: MSs – nomenclature of medical services, BP – blood pressure, ALT – alanine aminotransferase, AST – aspartate aminotransferase, MV – mechanical ventilation, LDH – lactate dehydrogenase, UFH – unfractionated sodium heparin**, CVP – central venous pressure.

Stages of cardiogenic shock depending on clinical severity and response to treatment

Stages of cardiogenic shock	Clinical characteristic
Preshock	The patient has no signs or symptoms of cardiogenic shock, but is at risk of developing it – acute MI, signs of acute heart failure, or decompensated chronic heart failure
Manifest cardiogenic shock	Signs of tissue hypoperfusion. Moist rales in the lungs. Urine output less than 30 ml/h. Lactate level of 2 mmol/L or higher. Invasive hemodynamic monitoring shows a cardiac index below 2.2 L/min/m², PCWP above 15 mm Hg.
Refractory cardiogenic shock	Condition of patients with shock symptoms and signs similar to the previous stage, but not improving or worsening with treatment. Lactate level remains above 2 mmol/L and is increasing. Liver and kidney function parameters are worsening.

Notes: PCWP – pulmonary capillary wedge pressure, MI – myocardial infarction, AHF – acute heart failure, CI – cardiac index, CHF – chronic heart failure.

Stages of cardiogenic shock according to the Society for Cardiovascular Angiography and Interventions (SCAI) classification

Stages of cardiogenic shock	Patient characteristics
E (extremis)	Patients in cardiac arrest undergoing ongoing cardiopulmonary resuscitation with active resuscitation using all available modalities, including ECMO
D (deteriorating)	Patients with signs of cardiogenic shock refractory to therapy for 30 minutes
C (classic)	Patients with hypoperfusion requiring evaluation and correction of volume status and treatment (inotropic, vasopressor, or mechanical circulatory support, ECMO)
B (beginning)	Patients with MI presenting with hypotension without signs of hypoperfusion
A (at risk)	Patients with acute MI

Notes: Adapted from [374]. MI – myocardial infarction, ECMO – extracorporeal membrane oxygenation.

Main contraindications to exercise training:

- Acute coronary syndrome;

- acute and subacute left ventricular aneurysm confirmed by instrumental diagnostic methods;

- presence of intracardiac thrombi;

- heart failure NYHA functional class IV NYHA;

- cardiac rhythm disorders (high-risk ventricular premature beats and tachycardia, paroxysmal tachyarrhythmias provoked by physical exertion) refractory to optimal medical therapy;

- conduction disorders (second- and third-degree sinoatrial and AV blocks, except for patients with implanted pacemakers**);

- uncontrolled hypertension (> 180/110 mmHg; a drop in systolic blood pressure ≥ 20 mmHg during physical exertion);

- severe aortic stenosis;

- severe obstructive hypertrophic cardiomyopathy;

- acute pericarditis, myocarditis, endocarditis;

- aortic dissection;

- syncope;

- thromboembolism or thrombophlebitis (within the past 3 months);

- stroke or TIA (within the past 3 months);

- uncontrolled diabetes mellitus;

- acute infectious disease (including viral infections);

- musculoskeletal disorders;

- severe comorbid conditions.

Appendix B. Physician Action Algorithms

Appendix B1. Choice of reperfusion in a patient with STEMI

Notes: CA — coronary angiography; LVT — thrombolytic therapy; PCI — percutaneous coronary intervention (usually with stenting).

* from diagnosis to crossing the infarct-related artery with a guidewire;

** preferably within the first 60 minutes and a maximum of the first 90 minutes from diagnosis, preferably in centers with a 24/7 primary PCI program; if primary PCI cannot be performed within the first 60 minutes of patient admission to a PCI center (and/or within the first 120 minutes from prehospital diagnosis), in-hospital thrombolytic therapy may be considered

*** preferably in the prehospital setting, within 10 minutes of diagnosis.

Appendix B2. Reperfusion options and time delays in STEMI

Notes:

IRA — infarct-related artery; CA — coronary angiography; STEMI — ST-segment elevation myocardial infarction; FMC — first medical contact; EMS — emergency medical services; LVT — thrombolytic therapy; PCI — percutaneous coronary intervention; PCI-c — center with percutaneous coronary intervention capabilities; non-PCI-c — center without percutaneous coronary intervention capabilities.

Notes:

1. SYMPTOM ONSET

The time from the patient's call for an emergency medical services (EMS) team to its arrival must not exceed 20 minutes.

2. First Medical Contact — DIAGNOSIS

The initial contact between a patient with suspected STEMI and medical personnel is designated as first medical contact (FMC). FMC can be performed by an EMS team, physicians at a hospital with percutaneous coronary intervention capabilities (PCI-c), or physicians at a hospital without percutaneous coronary intervention capabilities (non-PCI-c). The time from FMC to STEMI diagnosis in each of the three scenarios must not exceed 10 minutes. This time is required to record and interpret the electrocardiogram (ECG).

3. SELECTION OF REPERFUSION STRATEGY and 4. REPERFUSION

Once the diagnosis is established, a reperfusion strategy must be selected (primary percutaneous coronary intervention [pPCI] or thrombolytic therapy [LVT]):

- if the EMS or non-PCI-c personnel estimate that the time from STEMI diagnosis to crossing the infarct-related artery (IRA) with a guidewire will not exceed 120 minutes, pPCI strategy should be chosen and LVT should not be performed. This time interval includes transport time (no more than 60 minutes) and the time from diagnosis/confirmation at the PCI center to crossing the infarct-related artery (IRA) with a guidewire (no more than 60 minutes);

- if, following a STEMI diagnosis by the EMS team, the patient is admitted to a non-PCI-c, and the estimated time from diagnosis to crossing the infarct-related artery (IRA) with a guidewire (i.e., to pPCI) does not exceed 120 minutes, the patient must be transferred to a PCI-c, with the time from admission to the non-PCI-c to the start of transport to the PCI-c not exceeding 30 minutes;

- if the EMS or non-PCI-c personnel estimate that the time from diagnosis to crossing the infarct-related artery (IRA) with a guidewire (i.e., to pPCI) will exceed 120 minutes, and no more than 12 hours have passed since symptom onset, the patient is indicated for thrombolytic therapy;

- if the EMS physicians or non-PCI-c physicians estimate that the time from diagnosis to crossing the infarct-related artery (IRA) with a guidewire (i.e., to pPCI) will exceed 120 minutes, but more than 12 hours have passed since symptom onset, the patient is transferred to a PCI-c;

- when the patient is admitted to a PCI-c and the time from symptom onset does not exceed 48 hours, pPCI is performed;

- if the time from symptom onset exceeds 48 hours and the patient is asymptomatic (no symptoms of ischemia, hemodynamic instability, life-threatening rhythm and conduction disorders, etc.), routine PCI is not performed;

- if the time from symptom onset exceeds 48 hours and there are symptoms of ischemia, hemodynamic instability, or life-threatening rhythm and conduction disorders, pPCI is performed;

- after patient transfer to a PCI-c, the time from diagnosis/confirmation at the PCI-c to crossing the IRA with a guidewire must not exceed 60 minutes;

- if LVT is chosen as the reperfusion method, the time from decision-making to the administration of the thrombolytic agent must not exceed 10 minutes;

- following the administration of the thrombolytic agent by the EMS team or non-PCI-c physicians, the patient must be transferred to a PCI-c as early as possible.

5. ASSESSMENT OF REPERFUSION CRITERIA (DURING LVT) and PCI after LVT

- 60–90 minutes after thrombolysis, achievement of reperfusion should be assessed based on ECG (ST-segment reduction >50% in leads with maximal ST-segment elevation);

- if reperfusion is not achieved (at least one reperfusion criterion is absent), rescue PCI must be performed as early as possible;

- if reperfusion is achieved (all reperfusion criteria are present), coronary angiography and, if necessary, PCI should be performed between 2 and 24 hours from the start of thrombolysis.

Appendix B3. Workflow algorithm for the cardiac intensive care unit and the Department of X-ray Surgical Diagnostic and Treatment Methods in cardiogenic shock when ECMO is available in the hospital

Receiving information about the upcoming admission of a patient with cardiogenic shock (call from the admission department).
Ensuring that the X-ray operating room of the endovascular interventions department remains unoccupied until the need for ECMO is determined for the incoming patient with cardiogenic shock.
Patient admission to the hospital, joint patient examination by an intensive care physician of the acute myocardial infarction ICU, a cardiologist of the acute myocardial infarction ICU, the responsible intensive care physician, and the on-duty physician of the X-ray surgical methods department.
Decision-making on treatment tactics: revascularization without mechanical support or revascularization with mechanical support (ECMO).
Performing a focused echocardiography examination with assessment of hemodynamic parameters.
Transfer of the patient to the X-ray surgical methods department.
Insertion of the ECMO system.
Performing angiography and myocardial revascularization (preferably complete revascularization).
Subsequent patient management in the ICU in accordance with standards and protocols.
Insertion of a pulmonary artery catheter.
The decision regarding the need for intra-aortic balloon counterpulsation (IABC) system insertion should be made 3 hours after ECMO initiation if there are signs of left ventricular volume overload (echocardiographic signs, high pulmonary capillary wedge pressure).

Appendix B4. Prehospital algorithm of actions for an ambulance physician or paramedic in STEMI

1. Collection of complaints and medical history, assessment of pain syndrome, physical examination, monitoring of hemodynamic parameters (BP, HR).

2. Restriction of physical activity.

3. ECG recording in at least 12 leads and implementation of remote ECG consultation (if necessary and feasible).

4. Initiation of continuous ECG monitoring, securing intravenous access, readiness for defibrillation and cardiopulmonary resuscitation.

5. Determination of the reperfusion therapy strategy.

(A) Primary PCI strategy, if the expected time from diagnosis to guidewire insertion into the occluded coronary artery is less than 120 minutes (alternatively – transport time no more than 60 minutes). In this case, use of ASA** at a dose of 150-300 mg (chewed; do not take enteric-coated oral dosage forms). Additional administration of clopidogrel** at a dose of 600 mg or ticagrelor** at a dose of 180 mg is possible. At the same time, the failure to prescribe P2Y₁₂ inhibitors at the prehospital stage cannot be considered a medical error, since the superiority of prehospital administration of this drug group compared to in-hospital administration has not been proven.

(B) Prehospital fibrinolytic therapy (FLT) (if there are no contraindications), if timely primary PCI cannot be performed. Fibrin-specific thrombolytics are used (ATC group: Enzymes, B01AD). Single-bolus thrombolytics are preferred due to convenience and ease of administration. In addition to the thrombolytic, ASA** (chewed 150-300 mg), clopidogrel** (orally 300 mg, in patients older than 75 years – 75 mg), as well as anticoagulants (ATC group: Heparin group, B01AB) should be used. The drug of choice is enoxaparin sodium** (intravenous bolus in patients younger than 75 years, single subcutaneous injection); UFH can also be used (intravenous bolus and infusion).

(C) Absence of reperfusion treatment (contraindications for FLT, unavailability of primary PCI). In the absence of contraindications, consider the use of ASA** at a dose of 150-300 mg (chewed; do not take enteric-coated oral dosage forms). Platelet P2Y₁₂ receptor inhibitors and anticoagulants are not used.

6. Emergency hospitalization to a hospital included in the ACS patient routing system, preferably with the capability for urgent PCI (for patients with signs of shock or suspected mechanical complications of MI – urgent PCI or CABG). The receiving hospital should be informed about the transportation of a patient with STEMI.

7. Relief of pain syndrome.

In the absence of arterial hypotension and other contraindications – nitroglycerin** at a dose of 0.4–0.5 mg in the form of sublingual tablets or aerosol (spray). If symptoms do not disappear after 5 minutes and the drug is well tolerated, it can be used again. Due to the risk of arterial hypotension, blood pressure must be continuously monitored.

In case of intense pain syndrome or ineffectiveness of nitroglycerin, intravenous administration of a narcotic analgesic is necessary. The dose of the narcotic analgesic required for adequate anesthesia must be selected individually. The drug of choice is morphine**. Before use, 10 mg of morphine** is diluted in at least 10 ml of 0.9% sodium chloride solution**. Initially, 2–4 mg of the drug substance should be administered slowly IV. If necessary, administration is repeated every 5–15 minutes with 2–4 mg until pain relief is achieved or side effects occur that prevent dose escalation.

8. Treatment of acute heart failure, life-threatening cardiac arrhythmias and conduction disorders in accordance with section 3.4 of these Guidelines.

9. In the dispatch card and accompanying slip, indicate the time of ACS onset, time of first medical contact, time of ECG recording, note the treatment performed at the prehospital stage indicating drug doses, and the time of patient delivery to the hospital. If known, indicate the drugs taken by the patient in the preceding 24 hours, their administration time, and doses.

Appendix C. Patient Information

Myocardial infarction is the death of an area of the heart muscle due to insufficient oxygen delivery. In most cases, this occurs due to the sudden blockage of a large coronary artery of the heart by a thrombus. A thrombus typically forms on the surface of a ruptured atherosclerotic plaque.

In the early stages of myocardial infarction, the risk of serious and life-threatening complications of the infarction is elevated. These include cardiac arrest, cardiac rupture, and acute heart failure. Each of these complications can be fatal. Some of them can be managed by medical personnel who are next to the patient. This opportunity to reduce the risk of death determines the necessity of having medical personnel and special equipment nearby. Many of these complications are preventable. With rapid and high-quality opening of the coronary artery, it is possible to save a substantial part of the heart muscle and reduce the risk of fatal complications. Therefore, timely seeking of medical attention by a patient with a developing myocardial infarction is of paramount importance. In other words, if certain symptoms appear, you must urgently call an ambulance team. Myocardial infarction is characterized by the onset of pressing pain or discomfort behind the sternum that does not go away at rest or after taking nitroglycerin**. These sensations may spread to the neck, lower jaw, left arm, under the left shoulder blade, and into the upper abdomen. A specially trained medical worker can figure out the situation and decide what to do next. They will record an electrocardiogram and, if the result indicates the cessation of blood flow through a large coronary artery, will determine the possibility of its restoration. This can be either the immediate administration of a thrombus-destroying drug or urgent transportation to a medical facility where the patency of the coronary artery will be restored mechanically, and a specially designed framework (stent) will be installed inside the vessel. In any case, due to the danger of the aforementioned serious complications, the treatment of acute myocardial infarction is carried out in specially created units of medical facilities.

Myocardial infarction is generally a manifestation of the progression of atherosclerosis, which develops in all human arteries. Therefore, after discharge, there is a threat of recurrent myocardial infarction and vascular events in organs supplied by other arteries. Due to this threat, it is extremely important not to stop the treatment started in the hospital and to focus on eliminating factors contributing to the progression of atherosclerosis. Smoking should be stopped, regular physical activity ensured, a diet designed for such cases followed, excess weight eliminated, and by following doctor's recommendations, low blood cholesterol levels maintained with medications, sustainable normalization of blood pressure ensured (in the presence of arterial hypertension), and a normal blood sugar level maintained (in the presence of diabetes mellitus). In addition, in case of extensive heart muscle damage and/or complications of myocardial infarction, additional treatment prescribed by a doctor is required. It is known that premature discontinuation of necessary medications significantly increases the risk of recurrent myocardial infarction and death, and the onset of heart failure, which can significantly limit your daily activity. You must not stop taking medications without consulting your doctor. To reduce the risk of recurrent events (myocardial infarction, its complications), it is highly desirable for you to participate in a special rehabilitation program that includes regular dosed physical exertion, psychological support, and organization of risk factor control. Ask your doctor about your rehabilitation program, necessary drug therapy, and lifestyle changes.

If all recommendations are followed and you are regularly monitored by a doctor, your chances of warding off another myocardial infarction and its formidable complications are very high. Cooperate with your doctor, and everything will be fine.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Academic Research Consortium High Bleeding Risk Scale in planned/performed PCI and/or in patients requiring dual antiplatelet therapy

Original title: Academic Research Consortium for High Bleeding Risk

(ARC-HBR)

Source: Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J 2019;40:2632–2653. https://doi.org/10.1093/eurheartj/ehz372 [225].

Type (underline): rating scale, index, questionnaire, other (specify).

Purpose: standardized method for identifying patients at high bleeding risk who are scheduled for, or have undergone, PCI and/or require dual antiplatelet therapy.

Content:

Major criteria	Minor criteria
● Expected long-term oral anticoagulant therapy ● Severe or end-stage CKD (eGFR <30 mL/min/1.73 m²) ● Hemoglobin <110 g/L ● Spontaneous bleeding requiring hospitalization and/or blood transfusion within the preceding 6 months, or of any timeframe in case of recurrent bleeding ● Moderate or severe thrombocytopenia (<100.0 × 10⁹/L) ● Chronic hemorrhagic diathesis ● Liver cirrhosis with portal hypertension ● Active malignancy (excluding non-melanoma skin cancer) within the preceding 12 months ● History of spontaneous intracranial hemorrhage of any timeframe ● Traumatic intracranial hemorrhage within the preceding 12 months ● History of cerebral arteriovenous malformation ● Severe or moderate ischemic stroke within the preceding 6 months ● Recent major surgery or major trauma within the preceding 30 days ● Urgent major surgery in a patient receiving dual antiplatelet therapy	● Age ≥ 75 years ● Moderate CKD (eGFR 30–59 mL/min/1.73 m²) ● Hemoglobin 110–129 g/L for men and 110–119 g/L for women ● Spontaneous bleeding, requiring hospitalization and/or blood transfusion within the preceding 12 months, not meeting the major criterion ● Long-term oral use of non-steroidal anti-inflammatory drugs or glucocorticoids ● Any ischemic stroke regardless of timeframe, not meeting the major criterion

Major criteria

Minor criteria

● Expected long-term oral anticoagulant therapy

● Severe or end-stage CKD (eGFR <30 mL/min/1.73 m²)

● Hemoglobin <110 g/L

● Spontaneous bleeding requiring hospitalization and/or blood transfusion within the preceding 6 months, or of any timeframe in case of recurrent bleeding

● Moderate or severe thrombocytopenia (<100.0 × 10⁹/L)

● Chronic hemorrhagic diathesis

● Liver cirrhosis with portal hypertension

● Active malignancy (excluding non-melanoma skin cancer) within the preceding 12 months

● History of spontaneous intracranial hemorrhage of any timeframe

● Traumatic intracranial hemorrhage within the preceding 12 months

● History of cerebral arteriovenous malformation

● Severe or moderate ischemic stroke within the preceding 6 months

● Recent major surgery or major trauma within the preceding 30 days

● Urgent major surgery in a patient receiving dual antiplatelet therapy

● Age ≥ 75 years

● Moderate CKD (eGFR 30–59 mL/min/1.73 m²)

● Hemoglobin 110–129 g/L for men and 110–119 g/L for women

● Spontaneous bleeding,

requiring hospitalization

and/or blood transfusion within the preceding 12 months, not meeting the major criterion

● Long-term oral use of non-steroidal anti-inflammatory drugs or glucocorticoids

● Any ischemic stroke regardless of timeframe, not meeting the major criterion

Key (interpretation): a high bleeding risk is indicated by the presence of at least one major or two minor criteria.

Explanatory notes: eGFR – estimated glomerular filtration rate, CKD – chronic kidney disease, PCI – percutaneous coronary intervention.

Appendix G2. Assessment of adverse event risk in STEMI patients after discharge (for decision-making regarding early discharge using the Zwolle score*)

Risk factor	Points
Heart failure class by Killip
II	4
III	9
IV	9
Infarct-related artery blood flow (TIMI)
0	2
1	2
2	1
Age
Age 60 years or older	2
Three-vessel disease on coronary angiography
Three-vessel disease on coronary angiography	1
Prior MI (current STEMI is recurrent)
Prior MI	1
Ischemia duration > 4 hours
Myocardial ischemia duration > 4 hours	1
Result interpretation
Early discharge (within 72 hours of admission)	Total score
Possible	≤3
Not justified	≥4

Note: * — scale is intended for patients with STEMI undergoing primary PCI [70, 71, 500-502]

Skill based on this guideline

Recognize STEMI and choose reperfusion45 min · 12 cases · first 3 free Keep blood pressure stable: PDE-5 inhibitors and nitrates25 min · 4 cases · first 2 free

Scales and calculators from this guideline

Dopamine calculatorCalculation of dopamine infusion rate (mcg/kg/min → ml/h) with automatic Killip ClassificationAssessment of Heart Failure in Acute Myocardial Infarction NYHA functional classClassification of chronic heart failure severity Norepinephrine calculatorCalculation of norepinephrine infusion rate in ml/h based on dose in mcg/kg/min, weight Borg Scale (RPE 6–20)Subjective rating of perceived exertion Dobutamine calculatorCalculation of dobutamine infusion rate (mcg/kg/min → ml/h) with automatic ARC-HBRHigh Bleeding Risk (HBR) in PCI / antithrombotic therapy CHA₂DS₂-VAScStroke risk assessment in atrial fibrillation

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