Non-ST-segment elevation acute coronary syndrome: clinical guidelines

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 blockers

CVD – cardiovascular disease

IABP – intra-aortic balloon counterpulsation

IV – intravenous

HIV – human immunodeficiency virus

IVUS – intravascular ultrasound of the coronary arteries (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

P2Y₁₂ receptor platelet inhibitors - P2Y₁₂ receptor platelet inhibitors (ATC group: Platelet aggregation inhibitors excluding heparin, B01AC)

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***)

LVEDP – left ventricular end-diastolic pressure

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

LCA – left coronary artery

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)

UA – unstable angina

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 of the coronary arteries

CVA – cerebrovascular accident

PVR – peripheral vascular resistance

ICU – intensive care unit

AHF – acute heart failure

RCA – right coronary artery

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

AFL – atrial flutter

PE – pulmonary embolism

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

LDL-C – low-density lipoprotein cholesterol

Chol – cholesterol

CHF – chronic heart failure

CVP – central venous pressure

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

HR – heart rate

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

ECMO – extracorporeal membrane oxygenation

PM – pacemaker (dual-chamber rate-unresponsive implantable pacemaker***; dual-chamber rate-responsive implantable pacemaker***; single-chamber rate-unresponsive implantable pacemaker***; single-chamber rate-responsive implantable pacemaker***; triple-chamber (biventricular) implantable pacemaker***; dual-chamber rate-responsive MRI-conditional implantable pacemaker***)

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 bodily function, working capacity, and the ability to adapt to changing environmental and internal conditions arising from the impact of pathogenic factors, accompanied by concurrent changes in the body's protective-compensatory and protective-adaptive reactions and mechanisms [3].

Selective invasive treatment strategy for acute coronary syndrome without persistent ST-segment elevation on ECG – diagnostic coronary angiography to address the feasibility of immediate myocardial revascularization only upon the appearance or recurrence of myocardial ischemia (including during non-invasive stress tests) or the development of severe complications (acute heart failure, malignant ventricular arrhythmias) [4].

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 the exposure to a causal factor, preventive or therapeutic intervention, and all established changes in health status occurring as a consequence of the intervention [5].

Conflict of interest – a situation in which a medical or pharmaceutical worker, in the exercise of their professional duties, has a personal interest—whether acting personally or through a company representative—in obtaining material gain or another advantage that influences or may influence 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 [3].

Clinical trial – any investigation conducted on human subjects to identify or verify clinical and/or pharmacological effects of investigational products, and/or to identify adverse reactions to investigational products, and/or to study their absorption, distribution, metabolism, and excretion with the aim of assessing their safety and/or efficacy. The terms "clinical trial" and "clinical study" are synonyms [6].

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

Medicinal products – pharmacological agents in the form of dosage forms used for the prevention, diagnosis, treatment of a disease, rehabilitation, and for the preservation, prevention, or termination of pregnancy [7].

Medical intervention – types of medical examinations and/or medical manipulations, as well as artificial termination of pregnancy, performed by a medical worker or other employee authorized to carry out 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 [3].

Medical worker – an individual who has a medical or other education, works in a medical organization, and whose labor (job) duties include the implementation of medical activities, or an individual who is an individual entrepreneur directly engaged in medical activities [3].

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***.

ECG monitoring – remote observation of electrocardiographic data

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.

Emergency invasive treatment strategy for acute coronary syndrome without persistent ST-segment elevations on ECG – diagnostic coronary angiography within the first 2 hours after hospital admission to address the feasibility of immediate myocardial revascularization [4].

Unstable angina – newly onset or worsening angina where the severity and duration of ischemia are insufficient to develop acute myocardial ischemic injury (diagnosed when levels exceed the 99th percentile of the upper reference limit in patients without a baseline elevation of cardiac troponin in the blood, or an increase and/or decrease in cardiac troponin concentration > 20% when the baseline level is already stably elevated (variability was ≤ 20%)). The concept of "unstable angina" includes: a prolonged (more than 20 minutes) anginal attack at rest; or new-onset angina corresponding to at least Canadian Cardiovascular Society (CCS) functional class (FC) II; or worsening angina (progressive angina, crescendo angina) corresponding to at least CCS FC III; or angina appearing within the first 2 weeks after MI (post-infarction angina).

Coronary artery bypass grafting (CABG) – creation of a bypass anastomosis 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 the concentration of cardiac troponin in the blood that at least once exceeds the 99th percentile of the upper reference limit in patients without a baseline elevation of cardiac troponin, or its increase > 20% at a baseline elevated cardiac troponin level if it previously remained stable (variability was ≤ 20%) or was decreasing.

Acute myocardial infarction (MI) – acute myocardial injury resulting from myocardial ischemia.

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.

Acute coronary syndrome without persistent ST-segment elevation on ECG (NSTE-ACS) – newly manifested clinical signs or symptoms of myocardial ischemia when the ECG lacks persistent (duration > 20 minutes) ST-segment elevation in at least two contiguous leads and there is no newly onset left bundle branch block.

Delayed invasive treatment strategy for acute coronary syndrome without persistent ST-segment elevation on ECG – diagnostic coronary angiography to address the feasibility of immediate myocardial revascularization up to 72 hours after hospital admission.

Patient – an individual to whom medical care is provided or who has applied for medical care regardless of the presence of a disease and their condition [3].

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.

Early invasive treatment strategy for acute coronary syndrome without persistent ST-segment elevation on ECG – diagnostic coronary angiography to address the feasibility of immediate myocardial revascularization within the first 24 hours after hospital admission [4].

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

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

Symptom – a manifestation of a disease, a statistically significant deviation of a parameter from its normal limits, or the emergence of a qualitatively new phenomenon uncharacteristic of a healthy organism.

Syndrome – a stable cluster of symptoms sharing a common pathogenesis [8].

Condition – changes in the organism resulting from the impact of pathogenic and/or physiological factors that require medical care [3].

Bare-metal stent (BMS) – a coronary artery stent (coronary stent) without a drug coating (bare-metal, uncoated metal); represents a metallic framework made of a biologically inert material.

Drug-eluting stent (DES) – a coronary artery stent whose structures release an antiproliferative substance over a specified period after deployment, 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 estimated effect of a medical intervention is true [9].

Grade of recommendation (GoR) – the degree of certainty regarding the truth of the intervention effect and that following the recommendations will bring more benefit than harm in a specific clinical situation [9].

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 percutaneously introduced devices required for this procedure.

Staged revascularization – sequential (i.e., not simultaneous with the revascularization of the culprit CA segment responsible for the given NSTE-ACS) performance of procedures falling under the definitions of PCI and/or CABG, in any combination, during or after the index hospitalization, with the aim of achieving complete or maximal possible revascularization of the coronary bed.

CHA₂DS₂-VASc – a risk score for ischemic stroke in atrial fibrillation in patients without a mechanical heart valve prosthesis or moderate-to-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 suggesting 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, it 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 in the prehospital or early hospital stages and subsequently transforms into a diagnosis of "acute MI", "UA", or, based on differential diagnosis results, any other diagnosis, including non-cardiological ones [4].

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.

Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) — newly onset clinical signs or symptoms of myocardial ischemia in the absence of persistent (lasting more than 20 minutes) ST-segment elevation on the ECG in at least two contiguous leads and in the absence of newly onset left bundle branch block (LBBB).

MI – acute myocardial injury due to ischemia [10]. For the diagnosis of acute MI not related to PCI or coronary artery bypass grafting (CABG), documentation of a rise and/or fall of cardiac troponin concentration in the blood is required, with at least one value exceeding the 99th percentile of the upper reference limit in patients without a baseline elevation of cardiac troponin, or a rise and/or fall in cardiac troponin concentration > 20% if the baseline values are elevated and stable (variability ≤ 20%), in combination with at least one criterion of acute myocardial ischemia.

Criteria for myocardial ischemia:

• newly onset (or presumed newly onset) ischemic ECG changes;

• appearance of pathological Q waves on the ECG;

• imaging evidence of new regions of viable myocardium loss or regional wall motion abnormalities characteristic of an ischemic etiology;

• identification of intracoronary thrombus by coronary angiography (CA) or autopsy.

Detailed criteria for myocardial infarction are presented in Appendix A3. Diagnostic criteria for myocardial infarction [10].

ECG changes characteristic of myocardial ischemia:

1. Newly onset ST-segment elevations 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 must 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).

2. Newly onset ST-segment elevations at the J point of ≥0.1 mV in leads V₂–V₃ compared with a previously recorded ECG (in the absence of LV hypertrophy or LBBB).

3. Newly onset horizontal or downsloping ST-segment depressions of ≥0.05 mV in at least two contiguous ECG leads and/or T-wave inversions >0.1 mV in at least two contiguous ECG leads with a dominant R wave or an R/S ratio >1 [10].

Non-ST-segment elevation myocardial infarction (NSTEMI) – myocardial infarction in which, in the early stages of the disease, there is no persistent (lasting more than 20 minutes) ST-segment elevation on the ECG in at least two contiguous leads and no newly onset LBBB.

Unstable angina (UA) – new-onset or worsening angina pectoris, where the severity and duration of ischemia are insufficient to cause acute myocardial ischemic injury (diagnosed by a cardiac troponin level exceeding the 99th percentile of the upper reference limit in patients without baseline troponin elevation, or a rise and/or fall in cardiac troponin concentration > 20% when baseline values are stable and elevated [variability ≤ 20%]).

The concept of "unstable angina" includes: a prolonged (more than 20 minutes) anginal attack at rest; or new-onset angina of at least CCS class II according to the Canadian Cardiovascular Society classification; or worsening angina (progressive angina, crescendo angina) of at least CCS class III according to the Canadian Cardiovascular Society classification; or angina occurring within the first 2 weeks after MI (post-infarction angina).

These guidelines discuss diagnostic and therapeutic approaches not only during the period when differential diagnosis between NSTE-ACS and ST-segment elevation ACS or differential diagnosis within NSTE-ACS (NSTEMI and UA) is performed, but also after the nosological diagnoses (NSTEMI or UA) are established. Therefore, the recommendations given in this document for the diagnosis of "NSTE-ACS" also apply to "NSTEMI" and "UA".

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

ACS is typically the result of coronary artery (CA) thrombosis. A thrombus most commonly develops at the site of rupture of a so-called vulnerable (unstable) atherosclerotic plaque (AP) — characterized by a large lipid core, an abundance of inflammatory cells, and a thin fibrous cap; however, thrombus formation is also possible over an endothelial defect (erosion) of the CA overlying an AP. In many cases, acute thrombosis occurs at the site of an initially hemodynamically insignificant CA stenosis.

Unlike ST-segment elevation ACS, NSTE-ACS is not characterized by prolonged occlusion of a major CA causing transmural myocardial ischemia.

In the CAs of patients with NSTE-ACS, multiple "vulnerable" APs are frequently found, including those with disrupted surface structures. Due to the high risk of recurrent CA occlusions, such patients require a combination of local interventions (targeting the specific AP responsible for the clinical presentation of NSTE-ACS) 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 and even within the structures of the atherosclerotic plaque can be a source of emboli into the distal coronary vascular bed of the heart. Microvascular myocardial embolization in itself can lead to the formation of small foci of necrosis and/or contribute to the expansion of the primary necrotic zone. In addition, if coronary artery occlusion is eliminated, small thromboemboli can disrupt blood flow at the microcirculatory level, preventing the full restoration of myocardial blood supply (reperfusion).

NSTE-ACS can also be a consequence of coronary artery spasm, spontaneous coronary artery dissection, or non-atherosclerotic coronary artery embolization. Myocardial ischemia can be triggered or exacerbated by anemia, hypoxemia, inflammation, infection, fever, as well as metabolic or endocrine disorders (particularly hyperthyroidism). Spasm, dissection, and thrombosis of the coronary arteries, along with tachycardia and increased blood pressure (BP), can occur with the use of cocaine and certain other illicit substances.

In some patients with NSTE-ACS, ischemic damage and subsequent myocardial necrosis (myocardial infarction) develop, the size of which may vary. The consequence of the loss of a significant portion of active myocardium is the process of cardiac remodeling. The formation of a necrotic focus in the myocardium is accompanied by changes in the size, shape, and wall thickness of the left ventricle (LV), while the surviving myocardium experiences increased workload and undergoes hypertrophy. The pumping function of the remodeled LV deteriorates, leading to the development of heart failure. The presence of even small foci of ischemic myocardial necrosis indicates a high risk of an unfavorable disease course.

1.3 Epidemiology of the Disease or Condition

Circulatory system diseases (CSD) are the leading cause of death in the adult population of the Russian Federation (RF). In recent years, the share of CSD in the structure of mortality causes has been over 40%: 2019 – 46%, 2020 – 45%, 2021 – 38% (a decrease due to the high proportion of COVID-19 infection – 17%), 2022 – 44% of the total number of deaths. In the structure of mortality from CSD, IHD accounted for 42.3% in 2022. Approximately the same contribution of IHD to CSD mortality is recorded in most countries and regions [11]. In the same year, MI as a cause of death was registered in 48,911 people (5.9% in the structure of CSD mortality) [12].

According to monitoring data from the Ministry of Health, 438,315 cases of ACS were registered in the Russian Federation in 2022 (12.5% fewer than in 2021), including 150,845 cases of STEMI and 287,470 of NSTE-ACS. A diagnosis of acute MI (including recurrent) 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 — the same indicator was 17.7% in 2018. According to national registries in Europe, in-hospital mortality ranges from 4 to 12%. In-hospital mortality for ACS overall in the Russian Federation in 2022 was 5.6%, and for NSTE-ACS – 2.9%. It is obvious that mortality in non-ST-segment elevation myocardial infarction is much higher than in unstable angina, but a separate analysis was not conducted. In recent years, the ratio between STEMI and NSTEMI has been steadily changing towards an increase in the proportion of NSTEMI [13], mainly due to the laboratory detection of "additional" cases of NSTEMI among those that until recently were classified as UA. An objective prerequisite for this was the widespread use of cardiac trops, including those determined by high-sensitivity methods, to confirm acute myocardial injury.

The frequency of PCI in patients with NSTE-ACS remains low at 37%. It should be remembered that the risk of complications after NSTE-ACS, especially after NSTEMI, during long-term follow-up is just as high as after STEMI. This is confirmed by the results of the RECORD-3 registry and foreign data [14, 15]. Special attention should be paid to the possibilities of invasive treatment in patients with NSTE-ACS.

Despite apparent progress in the treatment of ACS, the medium-term and long-term prognosis remains generally unfavorable. According to observational studies, the incidence of major adverse cardiovascular events (cardiac death, recurrent MI, ischemic stroke) after MI is about 20%. Over the next 3 years, major adverse cardiovascular events are observed in another 20% of patients [16, 17]. Consequently, patients after MI/ACS belong to the category of very high risk for complications, which dictates the need for clinical follow-up and effective secondary prevention, both drug-based and non-pharmacological.

1.4 Features of Coding the Disease or Condition

I20.0 Unstable angina.

I21. Acute myocardial infarction

I21.0. Acute transmural myocardial infarction of the anterior wall

I21.1. Acute transmural myocardial infarction of the inferior wall

I21.2. Acute transmural myocardial infarction of other specified sites

I21.3. Acute transmural myocardial infarction of unspecified site

I21.4. Acute subendocardial myocardial infarction

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

I24.8. Other forms of acute ischemic heart disease

I24.9. Acute ischemic heart disease, unspecified

Most often, the outcome of the preliminary diagnosis of "NSTE-ACS" is the final diagnosis:

- "MI without the formation of pathological Q waves" (corresponding to categories I21.4, I22.0–I.22.8);

- "UA" (category I20.0).

In the event that NSTE-ACS progresses to MI with the formation of a Q wave on the ECG, codes I21.0–I21.2, I22.0–I22.8 are assigned.

In rare cases of death of a patient with NSTE-ACS (see criteria for type 3 MI according to the Fourth Universal Definition), category I24.8 should be used.

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 NSTEMI symptoms, the diagnosis of "MI" is no longer applied. 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:

1. ST-segment elevation ACS — ST-segment elevation myocardial infarction (not discussed in this document);

2. Non-ST-segment elevation ACS.

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

1. ST-segment elevation myocardial infarction (not discussed in this document);

2. Non-ST-segment elevation myocardial infarction;

3. Unstable angina.

Classification of MI based on subsequent ECG changes (optional):

1. MI with the formation of pathological Q waves;

2. MI without the formation of pathological Q waves.

Classification of MI based on the depth of myocardial layer involvement (prioritized for pathological/forensic autopsy diagnosis):

1. Subendocardial MI;

2. Transmural MI.

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

1. Left ventricular anterior wall MI (anterior MI);

2. Left ventricular lateral wall MI (lateral MI);

3. Apex myocardial infarction;

4. Left ventricular inferior wall MI (inferior MI);

5. LV posterior wall MI (posterior MI);

6. Interventricular septum MI;

7. Right ventricular MI;

8. Atrial MI;

9. Combined localizations are possible: posteroinferior, anterolateral, etc.

Classification of MI based on a history of MI:

1. Recurrent MI — MI developing after 28 days from the onset of the previous MI;

2. Reinfarction — MI developing within 28 days (inclusive) from the onset of the previous MI.

Classification of MI types:

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.

Criteria for the diagnosis and differential diagnosis of various types of MI are presented in Appendix A3. Diagnostic criteria for myocardial infarction [10].

Clinical variants of unstable angina:

1. Rest angina with a pain syndrome lasting more than 20 minutes;

2. New-onset angina pectoris corresponding to at least class II according to the Canadian Cardiovascular Society classification;

3. Worsening angina pectoris (progressive angina, syn.: crescendo angina) to at least class III according to the Canadian Cardiovascular Society classification;

4. Post-infarction angina (appearing in the first 2 weeks after MI).

Due to the fact that not every case of rest angina, new-onset angina, or worsening angina meets the criteria for UA, in cases of NSTE-ACS when MI is ruled out, the diagnosis is optimally formulated as "Unstable angina" (code I20.0).

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 ACS, symptoms are typically similar in nature to those occurring during an anginal attack, but differ in severity and duration; in some cases, symptoms are not completely relieved by the administration of nitroglycerin**, and sometimes even by repeated injections of narcotic analgesics. The intensity of the pain syndrome can vary from mild to excruciating; symptoms can be undulating in character and last from 20 minutes to several hours.

NSTE-ACS should be suspected in the following clinical situations: (1) prolonged (more than 20 minutes) anginal attack at rest; (2) new-onset angina corresponding to at least class II according to the Canadian Cardiovascular Society classification; (3) worsening of previously stable angina to at least class III according to the Canadian Cardiovascular Society classification (crescendo angina); (4) angina appearing in the first 2 weeks after MI (post-infarction angina).

In atypical clinical manifestations, depending on the dominant symptoms in patients with developing MI, the asthmatic variant, abdominal variant, arrhythmic variant, cerebrovascular variant, as well as the paucisymptomatic (painless) form are distinguished. Similar manifestations are possible in acute myocardial ischemia without MI formation. The clinical picture of NSTE-ACS may include, and sometimes predominate with, symptoms of its main complications—acute heart failure (pulmonary edema, cardiogenic shock), severe bradycardia or tachycardia, etc.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for diagnosing NSTE-ACS are presented in Section 1.5. Classification of the disease or condition (groups of diseases or conditions): clinical variants of unstable angina and Appendix A3 Criteria for the diagnosis of myocardial infarction.

2.1 Complaints and Anamnesis

In the initial diagnosis of NSTE-ACS, it is recommended to rely on the assessment of the nature of the pain syndrome and/or its equivalents. Irradiation of pain to the neck, lower jaw, and left arm is quite typical. However, in a number of patients, less characteristic symptoms may come to the fore – dyspnea, epigastric pain, nausea, dizziness, weakness, and others. A positive effect of nitroglycerin does not rule out NSTE-ACS.

Upon initial medical contact with a patient, it is recommended to rely on the clinical manifestations of the disease, ECG changes, and also to record the time from the onset of the pain episode to contact with a physician (medical worker). In certain cases of differential diagnosis with other conditions or diseases accompanied by ECG changes, one should focus on a detailed study of the characteristics of the pain syndrome, as well as data from other, primarily imaging (e.g., echocardiography (EchoCG), multislice computed tomography) and laboratory methods.

• In all patients with suspected NSTE-ACS, it is recommended to collect and evaluate complaints and anamnesis to determine the features of CHD exacerbation, perform differential diagnosis, identify symptoms that allow assessing the presence and severity of other diseases provoking or complicating the course of NSTE-ACS and capable of influencing the choice of treatment approaches, as well as to identify complications of NSTE-ACS [4].

ESC IC (LoE C, SoR 5)

Comments: Clinical manifestations of NSTE-ACS are diverse – from cardiac arrest, shock, life-threatening arrhythmias to minimal complaints in the form of slight retrosternal discomfort/dyspnea, and in some cases, the absence of any clinical symptoms. Up to 50% of patients referred to the hospital with NSTE-ACS will be discharged with another diagnosis, including one unrelated to cardiovascular diseases.

Pain sensations and discomfort in the cardiac region, apart from heart diseases, can be caused by pathology of other thoracic organs (lungs, pleura, mediastinum, diaphragm), digestive tract, musculoskeletal structures of the chest wall, nervous system diseases, as well as 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.

2.2 Physical Examination

• In all patients with suspected NSTE-ACS, it is recommended to perform a physical examination for differential diagnosis, to identify signs allowing to assess the presence and severity of other diseases provoking or complicating the course of NSTE-ACS and capable of influencing the choice of treatment approaches, as well as to assess the presence of NSTE-ACS complications [4, 18-20].

ESC IC (LoE C, SoR 5)

Comments: The main task of physical examination in patients with NSTE-ACS is to identify conditions indicating a high risk of an unfavorable in-hospital or long-term prognosis. These include manifestations of heart failure decompensation, auscultatory murmurs in the presence of concomitant heart defects or mechanical complications of MI, signs allowing to suspect pulmonary embolism (PE) or acute aortic syndrome, manifestations of gastrointestinal tract, central nervous system, and renal pathology.

2.3 Laboratory Diagnostics

• In all patients with suspected NSTE-ACS, it is recommended to test the dynamics of cardiac troponin T or I levels (according to the nomenclature of medical services: study of troponin I, T levels in blood; if impossible to perform, rapid testing of troponin I, T levels in blood), to confirm/exclude MI and assess the risk of an unfavorable outcome, with results obtained within 60 minutes after blood sampling [21–25].

ESC IB (LoE A, LoR 1)

Comments: High-sensitivity assay methods (i.e., allowing the detection of cardiac troponin in ~50–95% of healthy individuals) performed on automated analyzers provide higher diagnostic accuracy compared to point-of-care (POC) test 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 acquisition. A randomized study 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 troponin measurement with a standard POC test) led to a significant reduction in 30-day treatment costs and had a comparable rate of major adverse cardiovascular events when compared to the exclusion strategy under a standard emergency department protocol [26].

In general, automated high-sensitivity troponin assay methods are preferred, however, the rapidly developing POC testing system will soon force a reassessment of this preference when more thoroughly validated high-sensitivity POC tests become clinically available [4].

Assessment of cardiac troponin levels in blood is a more sensitive and specific method than the determination of the MB fraction of creatine phosphokinase or myoglobin. The latter is not recommended for use.

An acute elevation in blood cardiac troponin concentration is observed not only in patients with type 1 MI, but also in Pathogenetic variants of MI not associated with atherothrombosis, as well as in acute non-ischemic myocardial injury in a variety of other diseases and conditions (acute and chronic heart failure, pulmonary embolism, myocarditis, cardiomyopathies, acute aortic syndrome, sepsis, acute cerebrovascular accident (ACVA), poisoning, etc.).

• In the early stages after hospital admission, patients with NSTE-ACS are recommended to use validated algorithms involving the determination of blood cardiac troponin T or I concentrations using high-sensitivity methods (according to the nomenclature of medical services: determination of troponin I and T levels in blood) for rapid confirmation or exclusion of MI (repeat blood sampling at 1 hour, or 2 hours, or 3 hours—depending on the 0/1, 0/2, or 0/3 hour algorithm used) [27–49].

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

Comment: The elevation of blood cardiac troponin concentration to diagnostically significant levels occurs within 1 to 6 hours after the episode of myocardial ischemia, depending on the sensitivity of the method. Therefore, repeated assessment of this parameter is often required to identify diagnostically significant dynamics indicative of acute myocardial injury. In NSTE-ACS, changes in blood biomarker levels are used both to detect acute MI and to stratify the risk of adverse outcomes and make decisions regarding patient management strategy—choosing between invasive and non-invasive treatment approaches, and determining the timing of coronary angiography (CAG).

The use of high-sensitivity methods for determining blood cardiac troponin concentration is preferred as they possess greater diagnostic accuracy. For high-sensitivity methods of determining cardiac troponin in blood to detect acute MI, protocols with repeat testing at 1 hour, 2 hours (Appendix A3. Algorithm for the exclusion and confirmation of acute myocardial injury based on blood cardiac troponin levels determined by high-sensitivity methods upon admission and at 1 or 2 hours) [31–48] or 3 hours (Appendix A3. Algorithm for the exclusion and confirmation of acute myocardial injury based on blood cardiac troponin levels determined by high-sensitivity methods upon admission and at 3 hours) [48, 49] are recommended, provided that the diagnostic assay used is validated within the framework of these algorithms and has established threshold values. When blood analysis is performed within the first hour after pain onset, repeat assessment of cardiac troponin levels using a high-sensitivity method is recommended after 3 hours.

In patients with normal cardiac troponin levels upon two measurements and persisting clinical suspicion of ACS, additional determinations should be scheduled at later stages of the disease (at 3 hours and sometimes later, especially when using less sensitive methods for determining blood cardiac troponin concentration).

• In all patients with suspected NSTE-ACS, it is recommended to perform a complete blood count (CBC), general general-practice biochemical blood test (total protein, urea, total bilirubin, blood aspartate aminotransferase and alanine aminotransferase activity), and urinalysis as part of the initial examination upon hospital admission and, if necessary, subsequent dynamic monitoring during hospitalization [4, 18, 21-23].

ESC 1C (LoE C, GoR 5)

Comment: Detection of decreased levels of total hemoglobin, erythrocytes, and/or platelets in the blood is a sign of increased bleeding 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 NSTE-ACS, to assess the risk of ischemic and bleeding events and to ensure treatment safety, it is recommended to test blood creatinine levels upon hospital admission and subsequently when clinically indicated, with the calculation of the glomerular filtration rate, and in the case of prescribing direct oral anticoagulants, also the creatinine clearance (CrCl) [50-52].

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 medicinal products (the choice of renal function criterion is determined by the Instructions for Medical Use of the medicinal product). 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 bleeding events.

• In all patients with suspected NSTE-ACS, it is recommended to test fasting blood glucose, screen for diabetes mellitus (DM) (glucose metabolism testing; oral glucose tolerance test; blood glycated hemoglobin testing), and repeat blood glucose testing in case of a history of DM or hyperglycemia upon admission in order to assess the risk of an adverse outcome [53-56].

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

Comment: Blood glucose levels are also recommended for determining indications for the use of glucose-lowering drugs and choosing their dose. During hospitalization, blood glucose concentration should be reassessed when clinically indicated.

• Patients with NSTE-ACS as soon as possible after admission, preferably within the first 24 hours, are recommended to undergo a biochemical blood test to assess lipid metabolism disorders (determination of blood total cholesterol, LDL-C, HDL-C, and triglyceride levels) for subsequent comparison with lipid levels achieved using lipid-lowering drugs [18, 57].

ESC IC (LoE C, GoR 5)

Comment: It is necessary to determine at least the levels of cholesterol (Chol), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.

• In all patients with NSTE-ACS, to ensure treatment safety, it is recommended to determine blood electrolyte concentrations (minimally—blood potassium level testing, blood sodium level testing; optimally—blood potassium level testing, blood sodium level testing, serum total magnesium level testing) and, if clinically indicated, to study acid-base balance and blood gases with correction and reassessment in case of deviations from normal values [58, 597, 598].

ESC IIbC (LoE C; GoR 4)

Comment: During hospitalization, blood electrolyte concentrations should be reassessed when clinically indicated.

• All patients with NSTE-ACS admitted to the hospital are recommended to undergo a coagulogram (aPPT, prothrombin time, prothrombin index, fibrinogen), determination of the international normalized ratio (INR) in case of vitamin K antagonist therapy, as well as—to predict the risk of perioperative bleeding and blood loss volume—determination of the Rh factor, ABO blood group system, D antigen of the Rh system (Rh factor), and phenotype for C, c, E, e, Cw, K, k antigens. Determination of hepatitis B virus surface antigen (HBsAg) in the blood, hepatitis C virus antibodies in the blood, Treponema pallidum antibodies in the blood, human immunodeficiency virus HIV-1 IgM and IgG antibodies in the blood, and human immunodeficiency virus HIV-2 IgM and IgG antibodies in the blood in all patients with NSTE-ACS to rule out association with HIV infection and hepatitis [4, 625-633].

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

2.4 Instrumental Diagnostics

• Within 10 minutes from the start of initial medical contact with a patient with suspected ACS, to determine the type of ACS and perform differential diagnosis with other conditions, it is recommended to record a 12-lead ECG at the site of initial contact and interpret the electrocardiographic data by a qualified specialist (healthcare professional) [4, 59–65, 599].

ESC IB (LoE C, GoR 4)

Comment: If medical personnel at the site of initial medical contact encounter difficulties in interpreting the ECG at the recording location, decoding, description, and interpretation of the electrocardiographic data using telemedicine technologies are recommended. Repeat ECG recording at the stage of first medical contact may be advisable in case of changes in the nature of the pain syndrome or clinical presentation of ACS.

NSTE-ACS is characterized by the following ECG signs of myocardial ischemia: (1) transient (lasting less than 20 minutes) ST-segment elevation in at least two contiguous leads; (2) transient or persistent ST-segment depression (especially horizontal or downsloping) ≥ 0.05 mV in at least two contiguous leads; (3) T-wave inversion of more than 0.1 mV in at least two contiguous leads; pronounced (≥ 0.2 mV) symmetrical negative T waves in precordial leads strongly suggest acute myocardial ischemia. Non-specific signs include ST-segment displacement of less than 0.05 mV and T-wave inversion of less than 0.1 mV.

If changes in the 12 standard ECG leads are uninformative, and clinical data suggest myocardial ischemia, it is recommended to use additional leads, such as V₇–V₉, V₃R–V₄R [63, 64]. If the ECG is uninformative in patients with ongoing suspicion of ACS, with persistent or recurrent symptoms, to timely detect ischemic changes on the ECG, it is recommended to repeat the recording (e.g., at intervals of 15–30 min during the first hour) or initiate continuous remote electrocardiographic monitoring (ECG monitoring) with evaluation of ST-segment displacement in 12 leads [65].

The absence of ischemic changes on the ECG should not rule out the diagnosis of NSTE-ACS. An important diagnostic technique is comparison with an ECG recorded prior to the current episode.

• In all patients with suspected NSTE-ACS, it is recommended to promptly initiate continuous remote electrocardiographic monitoring until the diagnosis is excluded, in order to timely detect dangerous cardiac arrhythmias [4, 66].

ESC IC (LoE C, GoR 5)

Comment: In patients with ongoing or recurrent symptoms or signs presumably associated with myocardial ischemia (primarily chest pain), continuous remote electrocardiographic monitoring (ECG monitoring) with evaluation of ST-segment displacement in 12 leads is recommended, if technically feasible [65].

• In patients with NSTE-ACS, to timely detect dangerous cardiac arrhythmias and/or conduction disturbances, it is recommended to perform continuous remote electrocardiographic monitoring lasting up to 24 hours, or until successful percutaneous coronary intervention (PCI), or for more than 24 hours in patients at high risk of ventricular tachycardia (VT) and/or ventricular fibrillation (VF) [4, 66, 67].

ESC IC (LoE C, GoR 5)

Comment: The risk of VT and/or VF is increased in the presence of previously documented life-threatening cardiac arrhythmias; persistent or recurrent myocardial ischemia; GRACE 1.0 risk score > 140; left ventricular (LV) ejection fraction (EF) < 40% (according to some data < 35%), especially when combined; acute heart failure (AHF) associated with myocardial ischemia; mechanical complications of MI; suboptimal result of reperfusion therapy and complications during its performance; persistence of critical stenoses in coronary arteries other than the culprit coronary artery [68-70].

• In patients with unstable angina, it is recommended to perform continuous remote electrocardiographic monitoring if the risk of VT and/or VF is high or vasospastic myocardial ischemia is suspected, in order to timely detect dangerous cardiac arrhythmias [4, 66, 67].

ESC IIbC (LoE C, GoR 5)

• In patients with suspected NSTE-ACS, it is recommended to perform coronary angiography (CAG) to clarify the diagnosis, assess prognosis, determine indications for invasive treatment, and select the method of myocardial revascularization. The advisability of CAG and the urgency of its performance in NSTE-ACS are determined by the clinical presentation and the result of adverse outcome risk stratification [71, 72].

ESC IA (LOCE B, LOE 1)

Comments: The main objective of CAG is to determine indications for invasive treatment and select the method of myocardial revascularization. CAG can be useful (1) to identify the coronary artery and/or its segment responsible for the development of ACS, (2) to confirm the diagnosis of ACS (detection of occlusive or mural coronary thrombosis) or rule it out (detection of normal coronary arteries prompts the search for alternative causes of chest pain) with the possibility of avoiding unnecessary antithrombotic treatment, (3) to assess short- and long-term prognosis, especially in patients who have not undergone revascularization.

If CAG data are insufficient, intravascular imaging methods (intravascular ultrasound (IVUS) of the vessel wall, optical coherence tomography (OCT) of coronary arteries) are recommended to clarify the nature and localization of pathological lesions in the coronary arteries [4, 73-77, 164]. To clarify the functional significance of coronary stenoses, measuring fractional flow reserve (FFR) or instantaneous wave-free ratio is recommended [78-79, 167, 607].

• In all patients with suspected NSTE-ACS, it is recommended to perform transthoracic echocardiography (TTE) with mandatory assessment of LV EF to clarify the diagnosis, treatment approaches, differential diagnosis, and detection of complications [4, 80-84, 608].

ESC IC (LoE C, GoR 5)

Comment: TTE (at least a POCUS-assisted examination) should preferably be performed prior to invasive evaluation; however, if there are indications for emergency intervention, its performance should not delay the patient's transfer to CAG. Emergency TTE is recommended for patients with acute heart failure (AHF), suspected mechanical complications of MI (acute mitral regurgitation due to papillary muscle dysfunction, papillary muscle or chordal rupture, ventricular septal defect (VSD), LV free wall rupture), ascending aortic dissection, cardiac tamponade, heart valve dysfunction (aortic stenosis, mitral regurgitation), as well as in case of an uninformative ECG (LBBB, pacemaker rhythm, etc.). Additional lung and inferior vena cava ultrasound (duplex scanning of the inferior vena cava and portal system veins) allows the detection of subclinical signs of congestion (manifestation of heart failure).

In critically ill patients, it is advisable to use a formalized short TTE protocol (at least a POCUS-assisted examination) to screen for the main potential causes of hemodynamic instability. TTE is necessary to assess LV function and geometry (detecting signs suggesting myocardial ischemia or necrosis), as well as to recognize complications such as intracardiac thrombosis, cardiac rupture, heart valve dysfunction, right ventricular MI, and pericarditis. TTE plays a significant role in diagnosing Takotsubo syndrome. Assessing the dynamics of regional and global LV function helps determine treatment efficacy. In addition, TTE is necessary to determine the disease prognosis and assess the need for medications with a positive impact on prognosis [82-84]. In some cases, TTE helps clarify the localization of the coronary lesion associated with the current coronary artery disease exacerbation.

• If differential diagnosis is necessary in patients with suspected NSTE-ACS, or to detect comorbidities and/or complications, it is recommended to perform chest X-ray [85, 86].

ESC I C (LoE C, GoR 4)

Comment: If chest computed tomography (CT) is performed, chest X-ray is not required.

• Contrast-enhanced cardiac magnetic resonance imaging (CMR) in NSTE-ACS is recommended to be considered as an additional method to clarify the localization and extent of myocardial injury when its dimensions are relatively small, as well as for the differential diagnosis of myocardial lesions, if technically feasible [10, 87, 88].

ESC IC (RR S, ELD 5)

Comments: Contrast-enhanced cardiac MRI is not recommended as a routine diagnostic method for patients with NSTE-ACS. It allows confirmation of myocardial necrosis, differentiation between ischemic and inflammatory (myocarditis) etiology of the lesion, confirmation or exclusion of Takotsubo syndrome, and is the gold-standard 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 ionizing radiation. However, technical complexities limit its application in the early stages of hospitalization.

• Cardiac MRI is recommended in case of inadequate visualization of the LV apex by other methods in patients with a high pre-test probability of LV thrombus, provided technical feasibility [89, 90].

ESC IIaC (LOE C, GoE 4)

• To detect myocardial ischemia in patients with suspected NSTE-ACS without recurring chest pain episodes, without dynamic ischemic ECG changes, and without a diagnostically significant increase in blood cardiac troponin levels on repeat measurements (preferably using a high-sensitivity assay), it is recommended to perform a non-invasive stress test, repeating it if necessary (see Terms and Definitions) [91–97].

ESC IIaA (GPP A, LoE 2)

Comments: Non-invasive cardiac imaging stress tests are preferred over exercise ECG testing and are indispensable when baseline ECG changes preclude ischemia detection. Non-invasive stress testing is preferably performed within the first 72 hours of hospitalization, barring any contraindications.

In selected cases, myocardial scintigraphy can be used to detect myocardial ischemia if technically feasible [610, 611].

• Computed tomographic coronary angiography (CTCA) is recommended to rule out ACS in patients with a low probability of CAD in the absence of ischemic ECG changes and elevated blood cardiac troponin T or I levels [98–104].

ESC IIaA (LOE A, GoE 1)

Comments: CTCA is not recommended as a routine diagnostic test in NSTE-ACS. It should not be used to rule out ACS in patients with known coronary atherosclerosis and has limitations in the presence of severe coronary calcification, tachycardia, or irregular heart rate (HR). The clinical value of this method in patients with an implanted coronary stent or prior coronary artery bypass graft (CABG) surgery has not been established. Its utility when using high-sensitivity cardiac troponin assays remains unclear.

• When differential diagnosis of NSTE-ACS from other conditions (aortic dissection, PE, pneumothorax, pleurisy, etc.) is required, chest CT is recommended [18, 105].

RSC IC (LoE C, GoR 5)

2.5 Other Procedures

2.5.1. Risk Stratification for Adverse Outcomes

• For adverse outcome risk stratification and management strategy selection in patients with NSTE-ACS, it is recommended to perform a comprehensive assessment of medical history, clinical findings, ECG, echocardiography, blood cardiac troponin T or I levels (preferably via a high-sensitivity assay), renal filtration function (eGFR), and, in some cases, myocardial ischemia imaging modalities [21, 61, 106–112].

ESC IA (LOCR C, LOE 4)

Comments: Risk categories for adverse outcomes in NSTE-ACS and the criteria for assigning patients to each category are provided in Appendix A3. Adverse outcome risk categories in NSTE-ACS.

In addition to assessing the probability of adverse outcomes, risk stratification is necessary to identify patients who require emergency coronary angiography (CA), those who should undergo CA within the first 24 hours of hospitalization (or medical contact if NSTE-ACS developed in-hospital), and those whose need for CA requires considering the response to initial medical therapy and further diagnostic workup.

Furthermore, in patients with NSTE-ACS, ECG changes indicative of an occlusive coronary lesion should be taken into account (Appendix A3. ECG changes affecting the management of patients with NSTE-ACS). CA findings also serve as a basis for refining the adverse outcome risk grade.

• In patients with NSTE-ACS, it is recommended to use validated risk scores and scales, specifically the GRACE risk score, for adverse outcome risk stratification [106, 108, 112–123].

ESC IIaB (LOCE A, LE 2)

Comments: To assess prognosis in NSTE-ACS (Appendix A3. Adverse outcome risk categories in NSTE-ACS), it is recommended to use the GRACE score (Appendix G1. Adverse outcome risk assessment in NSTE-ACS using the GRACE score) [106, 114–119, 122]. When selecting management approaches for patients with NSTE-ACS, the GRACE 1.0 score is recommended. One of its versions allows risk stratification upon hospital admission, while another allows it at discharge.

The ARC-HBR score (Appendix G2) [123] can be used as an individual bleeding risk assessment tool in NSTE-ACS. In addition, the CRUSADE score (in-hospital major bleeding risk assessment in patients undergoing CA) (Appendix G3) [51] and the PRECISE-DAPT score (bleeding risk assessment in stented patients on dual antiplatelet therapy) [121] (Appendix G4) can be applied. There is also the domestic ORACLE bleeding risk score, applicable, inter alia, when combining antiplatelet agents with anticoagulants [52, 124–126] (Appendix G5).

In patients at high bleeding risk, measures to reduce this risk are recommended. A high bleeding risk should not automatically preclude the use of the most effective antithrombotic and invasive treatment strategies for NSTE-ACS. The choice of treatment approaches in patients at high bleeding risk must be personalized, taking into account the hazard of thrombotic complications, the feasibility of controlling potential bleeding sources, the benefit-risk ratio of each planned intervention, and all other clinical circumstances of the specific patient.

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

3.1. Invasive treatment of the disease

3.1.1. Selection of treatment strategy for NSTE-ACS patients in the hospital setting

• In patients with NSTE-ACS, to improve prognosis and control disease symptoms based on adverse outcome risk assessment, it is recommended to select and implement one of the in-hospital invasive management strategies: CA with the intent to perform myocardial revascularization (PCI or CABG) [71, 127–136].

ESC IA (LoE A, GoR 1)

Comments: The following invasive management strategies are recommended for patients with NSTE-ACS:

- immediate invasive strategy (CA with the intent to perform myocardial revascularization within the first 2 hours of hospitalization),

- early invasive strategy (CA with the intent to perform myocardial revascularization within the first 24 hours of hospitalization),

- selective (conservative/conservative-invasive) invasive strategy (initial medical therapy, with CA and intent to perform myocardial revascularization performed only upon recurrence of myocardial ischemia, development of complications, or in patients with a high likelihood of NSTE-ACS).

The choice of strategy is based on the presence of high and very high adverse outcome risk criteria (Appendix A3. Adverse outcome risk categories in NSTE-ACS).

• In patients with NSTE-ACS and at least one very high-risk criterion, it is recommended to perform CA with the intent to perform myocardial revascularization as early as possible after hospitalization (within the first 2 hours) to reduce the likelihood of adverse outcomes [4, 137].

ESC IC (LoE C, GoR 5)

Comments: Very high adverse outcome risk criteria include: hemodynamic instability or cardiogenic shock; ongoing or recurrent chest pain refractory to medical treatment; life-threatening arrhythmias or cardiac arrest; acute heart failure presumably related to ongoing myocardial ischemia; mechanical complications of acute MI (free wall rupture, ventricular septal rupture, papillary muscle or mitral valve chordae rupture); recurrent dynamic shifts (especially ST-segment elevation) or T-wave changes suggesting myocardial ischemia. An urgent invasive strategy must be implemented in such patients regardless of blood myocardial necrosis biomarker levels, ECG changes, and risk score values. Hospitals without emergency PCI capabilities must immediately transfer such patients to invasive centers.

If NSTE-ACS develops in-hospital, the time to CA should be measured from the moment of initial medical contact.

• In patients with NSTE-ACS classified as high risk, it is recommended to perform CA with the intent to perform myocardial revascularization prior to hospital discharge to reduce the likelihood of adverse outcomes [71, 128–134, 136, 138–147].

ESC IA (LoE A, GoR 1)

Comments: High adverse outcome risk criteria include: presence of NSTEMI; transient ST-segment elevation; dynamic ST-segment displacement or T-wave changes; GRACE 1.0 score sum >140 [128, 134, 139]. Hospitals without PCI capabilities must transfer such patients to invasive centers.

If NSTE-ACS develops in-hospital, the time to CA should be measured from the moment of initial medical contact.

• In high-risk NSTE-ACS patients, it is recommended to perform coronary angiography with the intent to perform myocardial revascularization within the first 24 hours of hospitalization to reduce the likelihood of recurrent myocardial ischemia and shorten the hospital stay [71, 128-134, 138-142].

ESC IIa A (RRR A, LOE 1)

Comments: High-risk criteria include: presence of NSTEMI; transient ST-segment elevation; dynamic ST-segment displacement or T-wave changes; GRACE 1.0 risk score >140 [128, 134, 139]. An invasive strategy within the first 24 hours of hospitalization in such patients does not affect mortality and MI rates, but leads to a significant reduction in the frequency of recurrent myocardial ischemia [142]. Hospitals without PCI capabilities must urgently transfer such patients to invasive centers. If coronary angiography with the intent to perform myocardial revascularization was not performed within the first 24 hours of hospitalization, the invasive treatment strategy should be implemented during the current hospital stay.

If NSTE-ACS develops in-hospital, the time to coronary angiography should be counted from the moment the patient seeks medical attention.

• In NSTE-ACS patients without recurrent myocardial ischemia and without criteria of very high and high risk of adverse outcomes, the decision regarding the appropriateness of pre-discharge coronary angiography and subsequent myocardial revascularization is recommended to be made based on the clinical presentation and results of additional examinations [71, 72, 92, 127-137, 140, 141, 143-150].

ESC IA (LoE A, GoR 1)

Comments: Additional examinations include: coronary CT angiography and non-invasive stress tests (preferably with myocardial perfusion imaging or assessment of contractility). In patients without recurrent myocardial ischemia, without criteria of very high and high risk of adverse outcomes, and with a high probability of NSTE-ACS, pre-discharge coronary angiography is preferred to address the appropriateness of myocardial revascularization.

• In all medical facilities providing care to NSTE-ACS patients, it is recommended to record and monitor the time intervals for performing invasive treatment specified in this document [4].

ESC IC (LoE C, SoR 5)

3.1.2. Methods of invasive treatment for NSTE-ACS patients

• In the majority of NSTE-ACS patients with single-vessel coronary artery disease, it is recommended to perform PCI of the infarct-related/symptom-related stenosis (occlusion) immediately after coronary angiography to reduce the risk of recurrent coronary events [4].

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

• In NSTE-ACS patients with multivessel coronary artery disease and absence of cardiogenic shock, in order to prevent recurrent ischemic events, it is recommended to consider complete revascularization within a single procedure, depending on technical capabilities, anatomical extent of coronary lesions, and the patient's clinical condition [151, 152].

ESC IIaC (LoE B, GoR 2)

• In NSTE-ACS patients with multivessel coronary artery disease, the choice between PCI and CABG is recommended to be made taking into account coronary anatomy, patient condition severity, and comorbidities, with potential use of the SYNTAX score. The decision is recommended to be made collectively by a cardiologist, cardiac surgeon, and an endovascular specialist [137, 147].

ESC IB (LoE C, GoR 5)

• When performing coronary angiography and PCI in NSTE-ACS patients, radial artery access is recommended as the preferred vascular access to reduce the risk of bleeding, death, major adverse cardiac events, and access-site complications, provided this access is proficiently performed at the given facility [153, 154].

ESC IA (LoE A, GoR 1)

• To reduce the risk of recurrent coronary events and the need for repeat revascularization in patients with NSTE-ACS undergoing primary PCI, it is recommended to prefer transluminal balloon angioplasty with coronary stenting over an isolated transluminal balloon angioplasty (without stenting) procedure of the coronary artery [155].

ESC IA (LoE A, GoR 1)

Comment: Meta-analyses have not revealed any superiority of coronary stenting over transluminal balloon angioplasty in reducing the risk of death. The majority of the evidence base indicating the superiority of PCI in reducing mortality in ACS was obtained using transluminal balloon angioplasty (without stenting). Therefore, one should not refrain from PCI in the form of transluminal balloon angioplasty on the grounds that suitable stents are unavailable.

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 angioplasty with coronary stenting in patients with NSTE-ACS, to reduce the risk of recurrent coronary events, stent thrombosis, and the need for repeat revascularization, it is recommended to use a next-generation drug-eluting stent (DES), regardless of the duration and composition of the planned antiplatelet and anticoagulant therapy [156-162].

ESC IA (LoE A, GoR 1)

• Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) of the coronary arteries is recommended to be considered as auxiliary tools during PCI in patients with NSTE-ACS to improve immediate and long-term outcomes of the intervention, provided technical capabilities are available [73-77, 163-165].

ESC IIaA (LoE A, GoR 2)

Comment: In a number of large meta-analyses and randomized trials, intravascular imaging (IVUS, OCT) has demonstrated a significant impact on the long-term outcomes of coronary stenting in terms of the prevention of stent thrombosis and restenosis. In one of the largest meta-analyses [166] comparing long-term outcomes in patients undergoing coronary stenting using various intravascular imaging methods, IVUS guidance led to a significant reduction in cardiovascular mortality, the incidence of recurrent MI, and stent thrombosis. Intravascular imaging can be useful for identifying the infarct(symptom)-related coronary lesion when angiographic data are inconclusive and for optimizing PCI.

• When determining the extent of myocardial revascularization during PCI in patients with NSTE-ACS and multivessel coronary disease in the absence of cardiogenic shock, it is recommended to consider assessing the functional significance of stenoses by measuring fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), provided technical capabilities are available [79, 152, 167-169, 607].

ESC IIaB (LoE C, GoR 4)

Comments: Measurement of fractional flow reserve (FFR) using hyperemic agents, such as #ATP (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 main coronary artery (LMCA) and 8-20 mg for the right coronary artery (RCA)) [600-603], and/or instantaneous wave-free ratio is the standard for assessing the functional significance of borderline (40-90%) coronary stenoses. An FFR value ≤ 0.8 is taken as the cutoff value (the stenosis is considered functionally significant). For the instantaneous wave-free ratio, this value is ≤0.89. Several studies have demonstrated the efficacy of FFR for assessing the functional significance of stenoses in this category of patients as well. The FRAME-AMI study [169] demonstrated the superiority of FFR in reducing overall mortality, recurrent MI, and unplanned revascularization. Conversely, the FLOWER-MI trial [170] did not demonstrate the superiority of FFR in reducing the incidence of major adverse cardiovascular events. Additionally, several observational studies have shown that patients with ACS may experience inaccurate functional assessment of lesion significance because microvascular recovery occurs no earlier than 24 hours after ACS onset [171, 172]. Since currently presented study results are contradictory, the appropriateness of using FFR in patients with ACS remains a subject for further study.

3.1.3. Renal protection during percutaneous coronary intervention

• In patients with NSTE-ACS and diabetes mellitus, it is recommended to take into account the higher risk of contrast-induced nephropathy, which must be considered when determining indications for procedures involving radiocontrast agents, choosing their volume, and deciding on active prophylaxis (hydration) when the patient's condition permits [173].

ESC I C (LoE C, GoR 4)

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

• In patients with NSTE-ACS and CKD, performing CAG and PCI is recommended after a careful risk-benefit assessment, taking into account the severity of renal filtration impairment [173].

ESC IB (LoE C, GoR 4)

• In patients with moderate or severe CKD undergoing an invasive treatment strategy for NSTE-ACS, hydration with isotonic sodium chloride solution** and the use of a low- or iso-osmolar contrast agent (in the minimal volume) are recommended for the prevention of acute kidney injury [174-180].

ESC IIaB (CQR A, LOR 2)

Comments: In patients with moderate or 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 possible) and for at least 24 hours after its completion (0.5 mL/kg/h for patients with LVEF ≤ 35% or NYHA class >2 heart failure). Hydration protocols guided by central venous pressure monitoring, or intravenous administration of #furosemide** with replacement of lost fluid volume 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.

3.1.4. 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 spontaneous coronary artery dissection (SCAD) do not differ from those in atherothrombosis; therefore, the primary strategy complies with standard recommendations for the management of patients with ACS (including NSTE-ACS). The most accurate methods to confirm SCAD during CAG are intravascular imaging modalities (IVUS and OCT).

• In complete coronary artery occlusion caused by SCAD, in the presence of patient hemodynamic instability, persistent signs of ischemia, and a high risk of cardiovascular events, standard PCI with stent implantation as the optimal revascularization strategy to restore coronary blood flow is recommended in patients with NSTE-ACS [181, 182].

ESC I C (LoE C, GoR 4)

Comment: 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, according to which IVUS or OCT should be considered to confirm SCAD (presence of a false lumen and/or intramural hematoma) as the cause of coronary artery obstruction [182, 183]. Intravascular imaging methods have high resolution and allow for the reliable establishment of dissection presence, its type, and the determination of the degree of lumen compromise and the position of the intracoronary guidewire (in the true or false lumen).

In patients with NSTE-ACS and SCAD without coronary artery obstruction, a low risk of recurrent events, and no signs of ischemia, medical therapy is recommended until the spontaneous dissection heals [182, 183].

3.1.5. Invasive Treatment Strategy in Patients with Cardiogenic Shock and Sudden Cardiac Arrest

• In patients with NSTE-ACS and cardiogenic shock, prompt myocardial revascularization is recommended to improve prognosis [184].

ESC IIa B (CARR B, LER 2)

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

• In patients with NSTE-ACS and cardiogenic shock, performing PCI with the restoration of blood flow in the infarct-related coronary artery, regardless of the time of symptom onset, is recommended [184, 185].

ESC IB (LoE B, LoR 2)

• In patients with NSTE-ACS and cardiogenic shock, due to the potential increased risk of death and acute kidney injury or rapid progression of CKD, it is recommended to refrain from simultaneous multivessel PCI, limiting the intervention to the infarct-related coronary artery [184, 185].

ESC IIIB (LOC B, LE Level 2)

• In patients with NSTE-ACS and cardiogenic shock in whom PCI is not feasible or has failed, emergency CABG is recommended to reduce the risk of death [184, 185].

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 versus initial medical stabilization. Anterior MI was noted in 60% of them, and multivessel coronary artery disease in 85% of cases. Among patients who underwent emergency revascularization, 64% underwent PCI and 36% underwent CABG. There was no difference in 30-day mortality (primary endpoint); however, 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 and, if possible, PCI. For patients with coronary anatomy unsuitable for PCI, emergency CABG is recommended.

• In patients with NSTE-ACS who have experienced cardiogenic shock and the index revascularization procedure, in the presence of ongoing ischemia, hemodynamic instability, and taking into consideration comorbidities, staged revascularization of non-infarct-related coronary arteries is recommended to improve prognosis [4].

ESC IIaC (LoE C, GoR 5)

• In hemodynamically stable patients with NSTE-ACS after successful resuscitation from sudden cardiac arrest, routine immediate CAG is not recommended [4, 186].

ESC IIIA (LE A, 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 CAG in patients without ischemic ECG changes was demonstrated in the COACT trial [186].

3.1.6. Myocardial infarction with non-obstructive coronary arteries

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a "working" diagnosis established in patients meeting the MI criteria according to the Fourth Universal Definition [10] (Appendix A3. Diagnostic Criteria for Myocardial Infarction) when CAG reveals no stenoses ≥ 50% in any major epicardial coronary artery. The term "MINOCA" encompasses a heterogeneous group of pathologies, both coronary and non-coronary, including non-cardiac ones. The main purpose of introducing this term is that a patient diagnosed with MINOCA requires further evaluation to verify the diagnosis and provide appropriate treatment.

• In patients with no obstructive coronary artery disease (stenoses ≥ 50% on CAG) 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 [169-171, 187].

ESC IC (LoE C, SoR 5)

Comment: The diagnostic workup in patients with MINOCA includes echocardiography, CAG using intravascular imaging modalities (IVUS or OCT) to rule out mural thrombi, erosions, and SCAD, testing for epicardial coronary spasm and microcirculatory obstruction, as well as, if necessary, additional tests for the differential diagnosis of ACS (the list of tests is determined by the 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 [170, 171, 187].

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

• In the absence of an obvious cause for MINOCA, cardiac MRI is recommended to clarify the etiology of myocardial injury [166, 172, 187-189].

ESC IB (LE B, LoE 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 NSTE-ACS, intravenous administration of morphine** (group N02AA – natural opium alkaloids; syn.: narcotic analgesics) is recommended [190-193].

ESC IIaB (LE C, LoE 4)

Comment: In most cases of unstable angina, the anginal attack can be relieved with nitrates. If the anginal pain does not subside within a few minutes after cessation of the triggering factor (physical exertion) or if it develops at rest, the patient should take nitroglycerin** (group C01DA – organic nitrates) at a dose of 0.4–0.5 mg as sublingual tablets or spray. If symptoms do not resolve within 5 minutes and the drug is well tolerated, it can be repeated. If chest pain or discomfort persists for 5 minutes after a repeated dose of nitroglycerin, emergency medical services must be called immediately. If 3 doses of nitroglycerin** do not reduce the intensity of the attack, further administration is pointless. Due to the risk of arterial hypotension, blood pressure must be continuously monitored.

A distinctive feature of anginal pain in myocardial infarction (MI), including NSTEMI, is a weak or absent response to nitroglycerin**. In addition to pain relief, morphine** helps reduce anxiety and agitation, decreases sympathetic activity, increases vagal tone, reduces the work of breathing, and causes dilation of peripheral arteries and veins (the latter being especially important in pulmonary edema). The dose required for adequate pain relief depends on individual sensitivity, age, and body size. Before use, 10 mg of morphine** is diluted in at least 10 mL of 0.9% sodium chloride** solution (group B05BB – solutions affecting the water-electrolyte balance). Initially, 2–4 mg of the drug substance should be administered IV slowly. If necessary, administration is repeated every 5–15 min 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 weakened primary effect of antiplatelet agents (clopidogrel**, ticagrelor**, prasugrel), which may affect treatment outcomes in some patients [194-195].

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

• severe arterial hypotension; resolved by placing the patient in a horizontal position with legs elevated (unless pulmonary edema is present). If this is insufficient, a 0.9% sodium chloride** solution is administered IV drip. In rare cases, adreno- and dopaminergic stimulants (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 agitation, the administration of tranquilizers (group N05BA – benzodiazepine derivatives) is recommended to relieve them in patients with NSTE-ACS [4, 196-198].

ESC IIaC (LoE C, GoR 5)

Comment: To reduce anxiety, 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 elderly patients is 2.5 mg; group N05BA – benzodiazepine derivatives). An appropriate staff behavioral style, 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 may also be prescribed. For agitation and delirium, intravenous administration of haloperidol** is quite effective and safe.

3.2.2. Correction of hypoxemia

• In patients with NSTE-ACS presenting with hypoxemia (blood hemoglobin oxygen saturation (SpO₂) < 90% or arterial blood partial pressure of oxygen (PaO₂) < 60 mmHg), inhalational oxygen administration (oxygen therapy) is recommended to correct it [4, 18].

ESC IC (RR S, ELD 5)

Comment: Humidified oxygen is delivered via nasal catheters at a flow rate of 2–8 L/min. Blood oxygen saturation is monitored by measuring SpO₂ non-invasively or by assessing blood gas parameters (primarily PaO₂) via laboratory tests.

• Due to the lack of beneficial effects on disease progression, inhalational oxygen administration (oxygen therapy) is not recommended for patients with NSTE-ACS with a blood oxygen saturation level (SpO₂) ≥ 90% [199-203].

ESC IIIB (LoE A, GoR 2)

Comment: Inhalational oxygen administration (oxygen therapy) is not only of no benefit to patients with uncomplicated NSTE-ACS, but may be harmful, presumably due to increased myocardial injury.

3.2.3. Antithrombotic therapy

In patients with NSTE-ACS at the initiation of treatment, a combination of ASA**, a platelet P2Y₁₂ receptor inhibitor, and an anticoagulant is recommended, followed by a transition to a combination of ASA** with a P2Y₁₂ receptor inhibitor, or to a combination of apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban, or indirect anticoagulants (vitamin K antagonists) with an antiplatelet agent [4, 204-239, 614-621].

ESC IA (LoE A, GoR 1)

Comments: Antithrombotic drugs and their doses are presented in Appendix A3. Pharmacological treatment of NSTE-ACS and Appendix A3. Doses of antithrombotic drugs in impaired renal function.

Indications for long-term anticoagulant therapy include atrial fibrillation/flutter, mechanical heart valve prosthesis***, left ventricular mural thrombosis, deep vein thrombosis, and/or pulmonary embolism.

3.2.3.1. Antiplatelet therapy in patients without indications for long-term oral anticoagulants

• To reduce the risk of death, MI, and ischemic stroke, all patients with NSTE-ACS without contraindications, regardless of the treatment strategy, are recommended to receive acetylsalicylic acid** (ASA**) indefinitely [4, 18, 204-209].

ESC IA (LoE A, GoR 1)

Comment: An initial (loading) dose of ASA** (group B01AC - platelet aggregation inhibitors excluding heparin) of 150–300 mg is recommended (chew and swallow the tablet); the permanent maintenance dose of ASA** is 75–100 mg orally once daily starting from the second day of patient treatment [4].

The initiation of ASA** therapy in NSTE-ACS in the pre-hospital setting lacks evidence of efficacy and safety (compared to its studied use in the hospital setting).

• In all patients with NSTE-ACS without a high bleeding risk, P2Y₁₂ platelet receptor inhibitors (clopidogrel**, ticagrelor**, prasugrel) are recommended in addition to ASA** for 12 months to reduce the cumulative risk of death, MI, and ischemic stroke [4, 18, 210-215].

ESC IA (CURL B, LOR 2)

Comments: The initiation of P2Y₁₂ platelet receptor inhibitors in NSTE-ACS in the pre-hospital setting lacks evidence of efficacy and safety (compared to their studied use in the hospital setting).

Premature discontinuation of dual antiplatelet therapy increases the rate of coronary events. A frequent cause of premature discontinuation of one or both components of dual antiplatelet therapy is bleeding and the need for surgical intervention. If it is necessary to discontinue a P2Y₁₂ platelet receptor inhibitor due to a surgical intervention, it is highly desirable to perform this intervention in a multi-profile hospital setting with the capability of performing PCI in the event of perioperative stent thrombosis and MI.

In the event of an emergency surgical procedure with a high bleeding risk or severe bleeding, treatment with a P2Y₁₂ platelet receptor inhibitor should be discontinued and resumed at the earliest opportunity after the causes of bleeding have been resolved.

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 it is impossible to adhere to these timeframes, the decision on surgical treatment should be made by a multidisciplinary medical board, which must evaluate the risks of bleeding and discontinuation of dual antiplatelet therapy, take into account the type of surgery, the risk of recurrent myocardial ischemia, the extent of coronary artery disease, the time elapsed since the onset of NSTE-ACS and PCI, and the characteristics of the implanted stents. For surgical procedures with a low bleeding risk, dual antiplatelet therapy should not be prematurely interrupted.

• If dual antiplatelet therapy (ASA** combined with a P2Y₁₂ platelet receptor inhibitor) in a patient with NSTE-ACS was delayed or interrupted due to CABG surgery, it is recommended to initiate or resume it after CABG surgery for at least 12 months to reduce the risk of ischemic events [298].

ESC IC (LoE C, SoR 5)

• In patients with NSTE-ACS and unknown coronary anatomy for whom an early invasive treatment strategy is planned (coronary angiography with the intent to perform myocardial revascularization within the first 24 hours of hospitalization), routine addition of a P2Y₁₂ platelet receptor inhibitor to ASA** prior to coronary angiography results is not recommended due to a potential increase in the risk of adverse outcomes [248-253].

ESC IIIA (LoE A, GoR 1)

• If invasive treatment (coronary angiography with the intent to perform myocardial revascularization) of a patient with NSTE-ACS is not planned within the first 24 hours of hospitalization and there is no high bleeding risk, it is recommended to add a P2Y₁₂ platelet receptor inhibitor (clopidogrel**, ticagrelor**, prasugrel) to ASA** to improve prognosis [214, 254].

ESC IIaB (CoE B, LOE 2)

Comment. This recommendation applies to patients with ongoing suspicion of NSTE-ACS, when coronary angiography can be performed later during hospitalization, as well as when non-invasive treatment of NSTE-ACS is planned.

• Prasugrel (loading dose 60 mg orally, daily maintenance dose 10 mg once daily orally) in addition to ASA** for 12 months is recommended for coronary stenting in patients with NSTE-ACS who have not received other P2Y₁₂ platelet receptor inhibitors, if there are no contraindications (history of intracranial hemorrhage, history of ischemic stroke or transient ischemic attack, active bleeding, severe hepatic impairment) to reduce the risk of ischemic events (composite of cardiovascular death, MI, and stroke; coronary artery stent thrombosis) [212, 248, 249, 255].

ESC IB (LoE B, GoR 2)

Comments: The safety of switching to prasugrel in patients already treated with clopidogrel** has not been sufficiently studied. Prasugrel treatment does not preclude the use of glycoprotein IIb/IIIa receptor blockers 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 NSTE-ACS, prasugrel is not recommended before diagnostic coronary angiography and the decision to perform PCI due to an increased bleeding risk [4, 249].

ESC IIIB (CGR B, LOR 2)

• Ticagrelor** (loading dose 180 mg orally, maintenance dose 90 mg orally twice daily) is recommended in addition to ASA** for 12 months in patients with NSTE-ACS regardless of the treatment strategy and prior clopidogrel** use, if there are no contraindications (history of intracranial hemorrhage, active bleeding) to reduce the risk of ischemic events (composite of cardiovascular death, MI, and stroke; coronary artery stent thrombosis) [4, 213, 256, 257, 623].

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

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

• In an early invasive treatment strategy for NSTE-ACS (coronary angiography with the intent to perform PCI within the first hours after hospital admission), it is recommended to prefer prasugrel over ticagrelor** for a more optimal effect on prognosis [248, 258].

ESC IIaB (LE B, LoE 2)

• In patients with NSTE-ACS who cannot receive ticagrelor** or prasugrel due to contraindications, intolerance, or unavailability, or who require long-term anticoagulant therapy, clopidogrel** (loading dose 300 or 600 mg orally, maintenance dose 75 mg orally once daily) is recommended in addition to ASA** for 12 months to reduce the risk of adverse outcomes (composite of cardiovascular death, MI, and stroke) [4, 18, 210, 211, 215].

ESC IB (LoE 5, GoR C)

Comments: If PCI is performed, a clopidogrel** loading dose of 600 mg is recommended; otherwise, a 300 mg loading dose is used.

• In elderly patients with NSTE-ACS, especially those at high bleeding risk, it is recommended to consider clopidogrel** (rather than ticagrelor** or prasugrel) in addition to ASA** to improve treatment adherence and reduce bleeding risk [259-261].

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 patients with NSTE-ACS, a high risk of subsequent ischemic events and a low bleeding risk, with no prior stroke or transient ischemic attack, following myocardial revascularization procedures (if indicated) and cessation of parenteral anticoagulant therapy, it is recommended to consider adding rivaroxaban** at a dose of 2.5 mg twice daily orally to the combination of ASA** and clopidogrel** for 12 months (in selected cases – up to 24 months) to reduce the risk of adverse outcomes (composite of cardiovascular death, MI, and stroke; coronary artery stent thrombosis***) [216, 604].

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

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 after the onset of NSTE-ACS treatment [216].

The addition of rivaroxaban** at a dose of 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 anticoagulants (particularly in the presence of atrial fibrillation (AF)).

• Intravenous administration of platelet GP IIb/IIIa receptor inhibitors (ATX group: Platelet aggregation inhibitors excluding heparin, B01AC) (abciximab, tirofiban, eptifibatide, FRaMon F[ab`]2 monoclonal antibody fragments) is recommended only as a bailout therapy in the event of thrombotic complications or the slow flow/no-reflow phenomenon during PCI [4, 262, 263].

ESC IIaC (LoE C, GoR 5)

Comments: GP IIb/IIIa receptor inhibitors were studied predominantly prior to the widespread use of platelet P2Y_12-receptor inhibitors [262, 263]. 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 platelet P2Y_12-receptor inhibitor, as well as in the presence of massive intracoronary thrombosis.

• In patients with NSTE-ACS and a high risk of gastrointestinal bleeding during dual antiplatelet therapy, proton pump inhibitors are recommended to protect the gastric mucosa and reduce the risk of gastrointestinal bleeding [264-268].

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, and 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** when combined with omeprazole** or esomeprazole**, but not with pantoprazole or rabeprazole, has been noted in laboratory assessments of platelet reactivity. There is no evidence that these drug interactions adversely affect clinical outcomes [266-270].

• Due to a high bleeding risk that outweighs the potential benefit, in patients with NSTE-ACS, ASA** is not recommended at a platelet count of less than 10×10⁹/L, clopidogrel** at less than 30×10⁹/L, and ticagrelor** or prasugrel at less than 50×10⁹/L [4, 271].

ESC III C (LoE C, GoR 5)

Alternative approaches to determining the duration and composition of dual antiplatelet therapy (combination of ASA** with a P2Y₁₂ platelet receptor inhibitor) during the first 12 months after NSTE-ACS

Assessment of ischemic and bleeding risks plays a major role in determining the duration of dual antiplatelet therapy in patients who have undergone NSTE-ACS.

• In patients with NSTE-ACS undergoing PCI without a high risk of ischemic events who have had no ischemic complications during dual antiplatelet therapy (combination of ASA** with a P2Y_12-receptor inhibitor), it is recommended to limit its duration to 3–6 months, switching to P2Y₁₂ receptor inhibitor monotherapy to reduce the risk of bleeding and indirectly reduce the risk of ischemic events [272-278].

ESC IIaA (LoE A, GoR 2)

Comments: Currently, the standard approach is a 12-month duration of dual antiplatelet therapy. The "early" switch 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.

• In patients with NSTE-ACS and a high bleeding risk, it is recommended to consider switching from the combination of ASA** and a P2Y_12-receptor inhibitor to P2Y₁₂ receptor inhibitor or ASA** monotherapy 1 month after initiation of treatment [279, 280].

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

Comments: Such an "early" switch from dual antiplatelet therapy to antiplatelet monotherapy appears safest regarding ischemic complications when discontinuing ASA** and switching to ticagrelor** monotherapy at 90 mg twice daily in patients undergoing PCI; switching to clopidogrel** monotherapy in patients with NSTE-ACS undergoing PCI was associated with an increased risk of myocardial infarction in the STOPDAPT-2 ACS trial [280].

• In patients with NSTE-ACS undergoing PCI who had no ischemic complications during the first month of dual antiplatelet therapy, it is recommended to consider switching from the combination of ASA** with ticagrelor** or prasugrel to the combination of ASA** with clopidogrel** ("de-escalation" of dual antiplatelet therapy) to reduce the risk of bleeding and the indirectly mediated risk of ischemic events [281-284].

ESC IIbA (CoE B, LOE 2)

Comments: To date, "de-escalation" of dual antiplatelet therapy by replacing prasugrel or ticagrelor** with clopidogrel** in the first month after ACS onset is not recommended. The approach to dual antiplatelet therapy "de-escalation" based on laboratory data (taking into account residual platelet reactivity, cytochrome P450 2C19 isoenzyme polymorphisms), studied in NSTE-ACS at earlier time points after PCI, has no advantages over de-escalation without laboratory guidance.

Possible grounds for switching from prasugrel or ticagrelor** to clopidogrel** in the first 12 months after NSTE-ACS: appearance or recurrence of clinically significant bleeding whose cause cannot be identified or eliminated; minor recurrent ("nuisance") bleeding from an unidentifiable source that affects treatment adherence; adverse effects of ticagrelor** (dyspnea, clinical manifestations of hyperuricemia); emergence of indications for long-term anticoagulant therapy; occurrence of ischemic stroke or TIA in patients receiving prasugrel; patient's desire to reduce the dosing frequency (switching from ticagrelor** to clopidogrel**) and the number of pills taken (switching from ticagrelor** or prasugrel to the fixed-dose combination of ASA** with clopidogrel**) to improve treatment adherence; limited availability of prasugrel or ticagrelor**, preventing their regular intake.

30 days after ACS treatment initiation, the following methods for switching from ticagrelor** or prasugrel to clopidogrel** are recommended: oral administration of 75 mg of clopidogrel** 24 hours after the last dose of prasugrel; oral administration of 600 mg of clopidogrel** 24 hours after the last dose of ticagrelor**. When switching to clopidogrel** due to bleeding or bleeding risk, it is recommended to consider initiating clopidogrel** with a maintenance dose (75 mg). Subsequently, the dose of clopidogrel** is 75 mg once daily.

3.2.3.2. Parenteral anticoagulants

• In patients with a confirmed diagnosis of NSTE-ACS, parenteral administration of anticoagulants (group B01A - antithrombotic agents) is recommended, unless contraindicated, to reduce the risk of adverse outcomes (composite of death and MI). When choosing a drug, one should consider the risk of ischemic events and bleeding, the patient's management strategy, and the efficacy and safety of the specific anticoagulant [217, 285].

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 NSTE-ACS development), parenteral administration of anticoagulants (including during PCI) is not recommended, provided that INR values ≥ 2.0 are maintained (≥ 2.5 during PCI).

In patients receiving direct oral anticoagulants, the use of an intravenous heparin sodium** bolus (syn.: unfractionated heparin (UFH)) during PCI is recommended 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 when INR < 2.5.

• Following successful PCI in patients with NSTE-ACS, it is recommended to discontinue parenteral anticoagulant administration due to the risk of increasing bleeding complications [4].

ESC IIa C (CGR C, LOR 5)

Comment: In patients with indications for long-term anticoagulant therapy (atrial fibrillation/flutter, mechanical heart valve prosthesis, left ventricular mural thrombus, prevention or treatment of venous thrombosis, pulmonary embolism), continuing parenteral anticoagulant administration at appropriate doses or considering a switch to oral anticoagulants is recommended. If myocardial revascularization was not performed and there are no indications for long-term anticoagulant therapy, parenteral anticoagulant treatment should be continued for up to 8 days (with earlier discontinuation if PCI was performed or the patient was discharged by this time); the minimum duration of parenteral anticoagulant administration in non-invasive management of NSTE-ACS is 2 days.

• When performing PCI within the first 24 hours of NSTE-ACS treatment, to reduce the risk of ischemic events, intravenous bolus administration of UFH** at a dose of 70–100 IU/kg is recommended [4].

ESC IC (LoE C, SoR 5)

Comments: When treatment is initiated prior to PCI, intravenous infusion of UFH** at a dose maintaining aPTT at 1.5–2.5 times the laboratory control value is recommended.

During PCI, UFH** should be administered intravenously as a 70–100 IU/kg bolus; 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.

• When performing coronary angiography within the first 24 hours of NSTE-ACS treatment, as an alternative to UFH** to reduce the risk of ischemic events, enoxaparin sodium** is recommended [220, 286-288].

ESC IIa B (LoE A, GoR 2)

Comments: Enoxaparin sodium** is not recommended when 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 patient with NSTE-ACS received enoxaparin sodium** prior to PCI, it should be continued during the procedure; moreover, if more than 8 hours have elapsed since the subcutaneous injection before balloon inflation in the coronary artery, an additional intravenous bolus of the drug at 0.3 mg/kg is recommended [220, 286, 612, 613].

ESC IIaB (CQR A, LOR 2)

• If coronary angiography is not planned in the early stages of NSTE-ACS treatment, fondaparinux sodium (2.5 mg subcutaneously once daily) is recommended to reduce the risk of ischemic events as it has the most favorable efficacy and safety profile, provided there are no contraindications [218, 219, 222].

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

Comments: A patient receiving fondaparinux sodium should be given intravenous UFH** during PCI—an initial bolus of 85 IU/kg; the need for repeat boluses is determined by the blood ACT value. Fondaparinux sodium is contraindicated when eGFR is below 20 mL/min/1.73 m².

If fondaparinux sodium is unavailable, enoxaparin sodium** may be used.

• In cases where a patient with NSTE-ACS has contraindications to both fondaparinux sodium and enoxaparin sodium** (e.g., due to severe renal filtration impairment), UFH** is recommended to reduce the risk of ischemic events [4].

ESC IB (LoE C, GoR 5)

3.2.3.3. Antithrombotic therapy in the presence of indications for long-term oral anticoagulation

• In patients with NSTE-ACS and indications for long-term anticoagulant therapy who were not taking them at the time of NSTE-ACS onset, it is recommended to initiate antithrombotic treatment with triple antithrombotic therapy (combination of ASA**, a P2Y₁₂ platelet receptor inhibitor, and a parenteral anticoagulant) followed by replacing the parenteral anticoagulant with an oral one (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban, or a vitamin K antagonist) [4, 204-239].

ESC IA (LoE 5, GoR C)

Comments: Indications for long-term anticoagulant therapy include atrial fibrillation/flutter, mechanical heart valve prosthesis, left ventricular mural thrombus, deep vein thrombosis and/or pulmonary embolism.

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 patients with NSTE-ACS and indications for long-term anticoagulant therapy who underwent coronary stenting, the duration of triple antithrombotic therapy (combination of an anticoagulant with ASA** and clopidogrel**) is recommended to be limited to a few days (1–7 days) to reduce the risk of hemorrhagic complications. After 1–7 days, following the discontinuation of ASA**, switching to dual antithrombotic therapy (oral anticoagulant combined with clopidogrel**) is recommended [230, 232-234, 289].

ESC IA (LoE A, GoR 2)

Comments: Clopidogrel** should be preferred over ASA** as part of dual antithrombotic therapy. In selected patients at very high risk of coronary stent thrombosis and low bleeding risk, the use of ticagrelor** instead of clopidogrel** for 6 months may be considered.

• In patients with NSTE-ACS and indications for long-term anticoagulant therapy who undergo coronary stenting and have a high risk of coronary events (including specific features of coronary anatomy and/or invasive intervention), in whom the expected benefit outweighs the bleeding risk, prolongation of triple antithrombotic therapy (a combination of an oral anticoagulant with ASA** and clopidogrel**) up to 1 month, followed by discontinuation of ASA** and switching to dual antithrombotic therapy (a combination of an oral anticoagulant with clopidogrel**), is recommended to reduce the risk of stent thrombosis [4, 233].

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

ESC IIaC (LoE C, GoR 5)

• In patients with NSTE-ACS requiring long-term anticoagulant therapy who did not undergo coronary stenting, the use of an oral anticoagulant combined with a single antiplatelet agent is recommended to reduce bleeding risk [233].

ESC IIaB (LoE B, GoR 2)

Comments: Prolonged triple antithrombotic therapy (a combination of an anticoagulant with two antiplatelet agents for more than 1 week) in patients who did not undergo coronary stenting is not recommended due to a high rate of bleeding, but may be considered on an individual basis in patients with a low bleeding risk and a very high risk of coronary events. Clopidogrel** or ASA** is recommended as the antiplatelet agent in combination with an oral anticoagulant in patients who did not undergo coronary stenting.

• In patients with NSTE-ACS and ongoing indications for anticoagulant therapy, dual antithrombotic therapy (an oral anticoagulant combined with clopidogrel**, less commonly with ASA**) is recommended for up to 12 months, after which clopidogrel** (or ASA**) is recommended to be discontinued, continuing monotherapy with an oral anticoagulant at the dose required for the prevention and/or treatment of thrombotic and/or thromboembolic events [204-239].

ESC IA (LoE A, GoR 2)

Comments: In patients with a high bleeding risk, switching to oral anticoagulant monotherapy 6 months after PCI is possible. A similar approach may be considered in NSTE-ACS 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 patients with NSTE-ACS and non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents, direct oral anticoagulants are recommended in preference to vitamin K antagonists, provided there are no contraindications [4].

ESC IB (LoE C, GoR 5)

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

• In patients with NSTE-ACS and non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents to prevent thromboembolic events, apixaban** at a dose of 5 mg twice daily or 2.5 mg twice daily (if indicated) is recommended, provided there are no contraindications [238].

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 ACS patients who underwent coronary stenting and in those managed non-invasively.

The standard dose of apixaban** in this clinical setting is 5 mg twice daily. If at least 2 of the following criteria are met – 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 NSTE-ACS and non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents to prevent thromboembolic events, dabigatran etexilate** at a dose of 150 mg twice daily or 110 mg twice daily is recommended, provided there are no contraindications [232, 237].

ESC IIa B (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 undergoing coronary stenting is safer than triple antithrombotic therapy (a combination of warfarin**, predominantly clopidogrel**, and ASA**). However, a trend towards a higher rate of coronary events was observed with the 110 mg twice daily dose of dabigatran etexilate**. Therefore, as part of dual antithrombotic therapy (in combination with clopidogrel**) after coronary stenting, dabigatran etexilate** at a dose of 150 mg twice daily is recommended; the 110 mg twice daily dose as part of dual antithrombotic therapy may be preferred in patients with a predominant bleeding risk. As part of triple antithrombotic therapy in non-valvular atrial fibrillation, the 110 mg twice daily dose is preferred.

• In patients with NSTE-ACS and non-valvular atrial fibrillation requiring a combination of anticoagulants and antiplatelet agents to prevent thromboembolic events, rivaroxaban** at a dose of 20 mg once daily (or 15 mg once daily if creatinine clearance is 30–49 mL/min) or 15 mg once daily (or #10 mg once daily if creatinine clearance is 30–49 mL/min) in patients with a predominant bleeding risk is recommended, provided there are no contraindications [4, 231, 624].

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

Comments: Rivaroxaban** at a dose of 15 mg once daily (or #10 mg once daily if creatinine clearance is 30–49 mL/min) combined predominantly with clopidogrel** in patients undergoing 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 NSTE-ACS and non-valvular atrial fibrillation receiving vitamin K antagonists combined with antiplatelet drugs, maintaining an INR of 2.0–2.5 with a time in therapeutic range (TTR) of at least 70% is recommended to reduce bleeding risk [227, 231, 235, 236, 237-239, 292].

ESC IIa B (LoE C, GoR 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 in case of thromboembolic events occurring within the specified INR range).

• To reduce the risk of bleeding during PCI in patients receiving oral anticoagulators, the radial approach is recommended [153, 154].

ESC IIa A (LoE A, GoR 1)

• In early invasive management of NSTE-ACS in patients receiving an oral anticoagulant, to reduce the risk of bleeding, the use of P2Y₁₂ platelet receptor inhibitors before coronary angiography and the decision to perform PCI is not recommended, and the utility of platelet glycoprotein IIb/IIIa receptor inhibitors should be considered only in case of obvious thrombotic PCI complications [4, 262, 263].

ESC IIIC (LE C, LoE 5)

• To protect the gastric mucosa and reduce the risk of gastrointestinal bleeding during triple antithrombotic therapy (a combination of an oral anticoagulant with a P2Y₁₂ platelet receptor inhibitor and ASA**) or dual antithrombotic therapy (a combination of an oral anticoagulant with a P2Y₁₂ platelet receptor inhibitor or ASA**) in patients at high risk for gastrointestinal bleeding, proton pump inhibitors are recommended [293-296].

RSC IA (LoE B, GoR 2)

Comment: 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 abuse.

It is known that the antiplatelet effect of clopidogrel** may be attenuated when combined with omeprazole** or esomeprazole**, but not with pantoprazole or rabeprazole, based on laboratory platelet function assays. There is no evidence that these drug-drug interactions adversely affect clinical treatment outcomes [264-270].

3.2.3.4. Antithrombotic therapy 12 months after NSTE-ACS in patients with no indication for long-term oral anticoagulant therapy

• In patients with NSTE-ACS who have a high risk of coronary events and a low risk of bleeding, and who have not experienced bleeding during the first year of treatment, extending dual antithrombotic therapy (a combination of ASA** with a P2Y₁₂ platelet receptor inhibitor or rivaroxaban** at a dose of 2.5 mg twice daily) for a longer period is recommended to reduce the risk of death, recurrent MI, and the composite risk of ischemic events. Furthermore, the benefit-risk ratio of extending dual antithrombotic therapy should be regularly reassessed during follow-up [4, 297-305].

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

Comments: A high risk of coronary events is indicated by the presence of coronary heart disease combined with one of the following criteria: diabetes mellitus requiring treatment; history of recurrent MI; multivessel coronary heart disease; combination of coronary and peripheral atherosclerosis; premature coronary heart disease (under the age of 45); accelerated development of coronary heart 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 the 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 remaining 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 patients with NSTE-ACS who are at high risk of coronary events and have not experienced bleeding during the first year of dual antiplatelet therapy, extending it as a combination of ASA** with a reduced dose of ticagrelor** (60 mg twice daily orally) is recommended to reduce the risk of ischemic events [303, 304].

ESC IIaB (LoE B, GoR 2)

Comments: In the PEGASUS-TIMI 54 trial, which demonstrated the feasibility of this approach, patients at high risk of coronary events 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, presence of diabetes mellitus requiring pharmacotherapy, two or more previous MIs, multivessel coronary atherosclerosis, CKD with an eGFR of less than 60 mL/min/1.73 m². The studied duration of using the combination of ASA** with ticagrelor** at a dose of 60 mg twice daily is 36 months.

• In patients with NSTE-ACS who are at high risk of thrombotic complications of atherosclerosis and have not experienced bleeding during the first year of treatment, long-term use of a combination of ASA** with rivaroxaban** at a dose of 2.5 mg twice daily orally is recommended to reduce the risk of ischemic events [305].

ESC IIaB (LoE B, GoR 2)

Comments: In the COMPASS trial [188], which demonstrated the feasibility of this approach, patients at high risk of thrombotic complications of atherosclerosis were defined as individuals with a history of MI or multivessel coronary atherosclerosis who were ≥ 65 years of age, 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 of less than 60 mL/min/1.73 m².

• In patients with NSTE-ACS, after 12 months, it is recommended to consider switching from ASA** monotherapy to P2Y₁₂ platelet receptor inhibitor monotherapy for an additional reduction in the risk of ischemic events [306, 307].

ESC IIbA (EOR B, EOR 2)

Comments: The additional benefit of clopidogrel** monotherapy is most evident in patients who underwent coronary stenting 1 year ago (the HOST-EXAM randomized controlled trial) [307]. Data favoring #ticagrelor** monotherapy at a dose of 90 mg twice daily have also been published (analysis of the GLASSY study within GLOBAL LEADERS) [308-309].

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 NSTE-ACS is not recommended [359, 310, 311].

ESC IIIB (LoE A, GoR 2)

Comment: In NSTE-ACS, nitrates are prescribed only according to indications, primarily post-infarction angina. Sometimes nitrates are prescribed for heart failure, although angiotensin-converting enzyme (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 drug 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 patients with NSTE-ACS and ongoing myocardial ischemia, arterial hypertension (AH), or heart failure in the absence of contraindications [312-314, 609].

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 systolic BP level, which should be reduced by 10–15% in normotensives and by 25–30% in individuals with AH, but not below 100 mm Hg. The usual starting 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 level cannot be achieved even after increasing the nitroglycerin infusion rate 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 nitroglycerin** infusion is usually sufficient due to the drug's short half-life. Standard measures to increase venous return to the heart are less frequently required (elevating the lower extremities; intravenous administration of 0.9% sodium chloride solution**, or the use of adrenergic and dopaminergic stimulants).

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

• In patients with NSTE-ACS, the use of organic nitrates is recommended when a vasospastic mechanism of ACS is suspected, as well as in proven vasospastic angina, for the relief and prevention of anginal attacks [310, 311, 313].

ESC IIaB (LoE B, GoR 2)

3.2.5. Beta-blockers

• In patients with NSTE-ACS, AH, and/or persistent myocardial ischemia, and/or tachycardia, without signs of acute heart failure (AHF), intravenous administration of a beta-blocker (preferably metoprolol**; Appendix A3. Pharmacological treatment of NSTE-ACS; Appendix A3. Doses of antithrombotic medications in impaired renal function) is recommended for ischemia control and prevention of ventricular arrhythmias in the absence of contraindications [315-321].

ESC IIaB (EOR A, EOR 1)

Comment: In patients with NSTE-ACS and no signs of AHF, it is recommended to administer an initial IV dose of a beta-blocker, especially in the presence of AH and/or persistent myocardial ischemia and/or tachycardia, followed by a transition to oral administration. IV beta-blockers prevent the development of life-threatening ventricular arrhythmias [322].

Evidence indicates that the benefit of beta-blockers is greater the earlier therapy is initiated and the faster its action is manifested.

• In NSTE-ACS, long-term oral beta-blocker therapy is recommended in patients with an LVEF ≤ 40%, regardless of the presence of heart failure, to reduce the risk of death, in the absence of contraindications [83, 315, 317, 323-327].

ESC IA (LoE A, GoR 1)

Comments: In this category of patients, it is recommended to continue or initiate one of three beta-blockers with a proven positive effect on mortality in chronic heart failure (CHF) with low LVEF (metoprolol** extended-release, bisoprolol** (group C07AB – selective beta-blockers), or carvedilol** (group C07AG – alpha- and beta-blockers)) or in MI with heart failure and low LVEF (carvedilol**), and, if well tolerated, to aim for target doses that provide a favorable effect on prognosis (Appendix A3. Pharmacological treatment of NSTE-ACS; Appendix A3. Doses of antithrombotic medications in impaired renal function).

Data on the efficacy of beta-blockers for improving prognosis after NSTE-ACS in patients with LVEF > 40% are inconclusive. A number of randomized trials are currently underway to evaluate the benefits of prescribing beta-blockers to patients with LVEF > 40% (BETAMI, DANBLOCK, REBOOT) and LVEF > 50% (REDUCE-AMI) [328-331]; their results may influence guidelines.

At the same time, the results of certain registries, retrospective studies, and meta-analyses indicate that the administration of beta-blockers improves prognosis [332-335], although not all registries report a clear benefit of prescribing beta-blockers to patients with preserved LVEF without heart failure [336-338]. Overall, it currently appears that benefit cannot be ruled out in all patients who have suffered NSTEMI, at least over the next 1 year.

In hemodynamically stable patients with NSTE-ACS, beta-blockers may be administered within the first 24 hours of symptom onset. In the early stages of NSTE-ACS, 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). Dose adequacy is usually assessed by the achieved heart rate. It should not fall below 44–46 beats per minute at night during rest.

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

Relative contraindications to the use of beta-blockers: clinical manifestations of heart failure, evidence of low cardiac output, systolic BP < 100 mm Hg, heart rate < 60 beats per minute, PR interval prolongation > 0.24 s, history of chronic obstructive pulmonary disease, 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.

3.2.6. Calcium channel blockers

• Due to the lack of evidence of efficacy in patients with NSTE-ACS, routine administration of calcium channel blockers is not recommended [339-351].

ESC IIIA (LoE A, GoR 1)

Comments: Due to the potential for uncontrolled hypotension in patients with NSTE-ACS, the use of short-acting nifedipine** (group C08CA – dihydropyridine derivatives) should be avoided [340-342].

• In patients with NSTE-ACS, recurrent myocardial ischemia, and contraindications to beta-blockers, verapamil** (or diltiazem in the presence of hypertension) is recommended for symptom relief, provided there is no clinically significant LV systolic dysfunction, increased risk of cardiogenic shock, PR interval duration > 0.24 s, or second- or third-degree AV block without a pacemaker [339, 343, 345, 348, 350, 351].

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

Comments: Verapamil**, diltiazem (group C08DA – phenylalkylamine derivatives), or amlodipine** (group C08CA – dihydropyridine derivatives) may be used when hypertension cannot be controlled by other means.

Diltiazem or verapamil** may be considered for heart rate control when beta-blockers cannot be used, and less frequently for terminating supraventricular tachyarrhythmias.

In patients with persistent myocardial ischemia when beta-blockers are insufficiently effective, contraindicated, or cause unacceptable complications, the addition of long-acting dihydropyridine derivatives may be considered.

Co-administration of verapamil** and diltiazem with beta-blockers is generally undesirable due to the cumulative risk of side effects.

• If vasospastic etiology of NSTE-ACS is suspected or vasospastic angina is proven, verapamil**, diltiazem, or long-acting dihydropyridine derivatives are recommended to relieve symptoms and prevent myocardial ischemia [352].

ESC IIaB (LoE C, GoR 5)

3.2.7. Renin-angiotensin-aldosterone system blockers

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

• In patients with NSTE-ACS and LVEF < 40%, hypertension, diabetes mellitus, or chronic kidney disease, ACE inhibitors are recommended to prevent LV dysfunction, heart failure, and death, unless contraindicated [82, 353-363].

ESC IA (LoE A, GoR 2)

Comments: In patients with acute NSTEMI, ACE inhibitor titration is recommended to start within the first 24 hours of treatment after hemodynamic stabilization. In patients with NSTEMI and/or LVEF ≤ 40%, it is recommended to use target doses of ACE inhibitors with a proven positive effect on prognosis. The dose should be gradually increased to the recommended (target) dose, or if not feasible, to the maximum tolerated dose (Appendix A3. Pharmacotherapy of NSTE-ACS; Appendix A3. Doses of antithrombotic drugs in impaired renal function).

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

• In all patients with NSTE-ACS, routine use of ACE inhibitors is recommended to reduce the risk of cardiovascular events, unless contraindicated [353, 354].

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

Comments: Randomized controlled trials in patients without known LVEF < 40% and heart failure have demonstrated the benefit of ramipril** and perindopril**.

• In patients with NSTEMI presenting with heart failure and/or low (≤ 40%) LVEF who are intolerant to ACE inhibitors, ARBs (preferably valsartan) are recommended for the treatment of heart failure, reduction of mortality risk, and prevention of heart failure progression [355, 364-366].

ESC IB (LoE B, LoR 2)

Comments: The starting dose of valsartan is 20 mg twice daily (40 mg/day); if well tolerated, the dose is gradually increased up to 160 mg twice daily.

• In patients with NSTEMI and low (≤ 40%) LVEF and/or signs of pulmonary congestion, valsartan/sacubitril** is recommended to reduce the risk of cardiovascular death and heart failure hospitalization [367-378].

ESC IIa B (LoE B; GoR 2).

Comment: According to the PARADISE-MI trial results, valsartan/sacubitril** (group C09DX – angiotensin II receptor blockers in combination with other drugs) was non-inferior to ramipril regarding the rate of death or hospitalization for worsening heart failure when administered in the early period (from 12 hours to 7 days) of NSTE-ACS [367-378]. In the PARADIGM-HF trial, valsartan/sacubitril** demonstrated superior efficacy compared to enalapril** in reducing the risk of death or hospitalization for worsening heart failure in patients with chronic heart failure and reduced LVEF [379].

Aldosterone antagonists

• In patients with NSTEMI with LV EF ≤ 40% combined with heart failure or diabetes mellitus, as well as in patients with UA and persistent heart failure NYHA class II-IV NYHA with LV EF ≤ 35%, without significant decline in renal filtration function and hyperkalemia, it is recommended to add an aldosterone antagonist, preferably eplerenone, to therapeutic doses of ACE inhibitors and beta-blockers to prevent heart failure and death [84, 380-382].

ESC IIa B (LoE A, GoR 2)

Comment: It is preferable to prescribe eplerenone within the first 3 days from NSTEMI onset. Contraindications to aldosterone antagonists: blood creatinine > 220 µmol/L in men, > 175 µmol/L in women, and serum potassium concentration > 5 mmol/L. During treatment with aldosterone antagonists, blood creatinine and potassium levels must be monitored. If serum potassium exceeds 5.5 mmol/L, the drugs should be discontinued. It is recommended to maintain serum potassium concentrations 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 NSTE-ACS regardless of baseline cholesterol levels, initiating or continuing high-dose 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy during hospitalization is recommended in the absence of contraindications [383-387].

ESC IA (LoE A, GoR 1)

Comments: The initial administration (first dose) of a high-dose HMG-CoA reductase inhibitor is recommended on the first day of hospitalization for NSTE-ACS and as early as possible. If percutaneous coronary intervention (PCI) is performed, the first dose of the HMG-CoA reductase inhibitor is recommended prior to the procedure to reduce the likelihood of cardiovascular complications and contrast-induced nephropathy following PCI [388, 389].

Both the indication for initiation and the starting dose of an HMG-CoA reductase inhibitor in NSTE-ACS are independent of total cholesterol and its fractions; therefore, initiation of an HMG-CoA reductase inhibitor should not be delayed while awaiting the results of a biochemical blood test.

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, typically within the first weeks of therapy initiation, and usually resolve rapidly after the HMG-CoA reductase inhibitor is discontinued. Rhabdomyolysis accompanied by a more than 10-fold increase in creatine kinase levels is extremely rare. An asymptomatic 3-fold or greater increase in transaminase levels may occur, necessitating a dose reduction or discontinuation of the drug with subsequent monitoring of hepatic transaminase activity. It should be borne in mind that in the acute phase of NSTE-MI, elevated transaminase levels are due to 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.

• For an additional reduction in the cumulative risk of ischemic events in patients with NSTE-ACS during hospitalization, it is recommended to consider initiating combination therapy with a high-dose HMG-CoA reductase inhibitor and ezetimibe (regardless of baseline cholesterol levels and its fractions and prior HMG-CoA reductase inhibitor therapy) [390].

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 administered in addition to prior statin therapy or concurrently with statins in statin-naive patients (two-thirds of the patients) and compared with statin monotherapy. Ezetimibe treatment was shown to be safe and to provide long-term cardiovascular outcome benefits [390].

• In patients with a history of NSTE-ACS, it is recommended to maintain low-density lipoprotein (LDL) cholesterol levels < 1.4 mmol/L while achieving a reduction of at least 50% from baseline values to ensure the maximal risk-reduction effect for recurrent ischemic events [122, 143, 387, 390].

ESC IA (LoE A, GoR 1)

Comments: Blood LDL cholesterol levels should be determined 4–6 weeks after initiation of treatment, following a dose change, or after the addition of a new lipid-lowering drug to evaluate 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** (ATC group C10AX – other lipid-lowering agents) or inclisiran) [390].

• In patients with NSTE-ACS who have experienced another vascular event (in any vascular bed) within the preceding 2 years in addition to the current NSTE-ACS, an LDL cholesterol target level of < 1.0 mmol/L is recommended to further reduce the risk of recurrent ischemic events [57, 391].

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

• In patients who, at the time of NSTE-ACS onset, were already taking an HMG-CoA reductase inhibitor at the maximally tolerated dose and ezetimibe, but present with LDL cholesterol levels above target upon admission, it is recommended to initiate early administration (during hospitalization for the current coronary event) of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor — alirocumab**, evolocumab**, or inclisiran — in addition to the maximally tolerated HMG-CoA reductase inhibitor and ezetimibe [392-395].

ESC IIaC for alirocumab and evolocumab,

RSC IIaC for inclisiran (LoE B, LoR 2)

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

• In the event of a marked increase (> 4.0 mmol/L) in LDL cholesterol levels in patients with NSTE-ACS, it is recommended to initiate early administration (during hospitalization for the current coronary event) of an HMG-CoA reductase inhibitor and ezetimibe [396].

RSC IIaA (LoE A, GoR 1)

• In the event of an extremely high increase (> 5.0 mmol/L) in LDL cholesterol levels in patients with NSTE-ACS, it is recommended to initiate early administration (during hospitalization for the current coronary event) of a maximally tolerated HMG-CoA reductase inhibitor + ezetimibe + a PCSK9 inhibitor (alirocumab**, evolocumab**, or inclisiran) [397-401].

RSC IIaA (LoE A, GoR 1)

• If a patient with a history of NSTE-ACS maintains a blood LDL cholesterol concentration above the target level while receiving the 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 cholesterol and the risk of ischemic events [390], including a fixed-dose combination tablet or capsule containing an HMG-CoA reductase inhibitor and ezetimibe.

ESC IIaB (LoE B, GoR 2)

Comment: This recommendation applies to patients who were not prescribed ezetimibe during hospitalization for NSTE-ACS in accordance with the in-hospital recommendation.

• If a patient with a history of NSTE-ACS maintains a blood LDL cholesterol concentration above the target level while receiving the maximally tolerated dose of an HMG-CoA reductase inhibitor combined with ezetimibe , it is recommended to add alirocumab**, evolocumab**, or inclisiran to further reduce blood LDL cholesterol and the risk of ischemic events [402-404].

ESC IB for alirocumab and evolocumab, RSC IB for inclisiran (LoE A, LoR 2)

Comments: If LDL cholesterol levels remain significantly elevated (> 2.5 mmol/L) despite therapy with maximally tolerated doses of HMG-CoA reductase inhibitors, the addition of alirocumab**, evolocumab**, or inclisiran may be considered without prior use of ezetimibe.

• In patients with NSTE-ACS or a history of NSTE-ACS who have an intolerance to HMG-CoA reductase inhibitors, it is recommended to consider the use of ezetimibe and/or a PCSK9 inhibitor drug (alirocumab**, evolocumab**, or inclisiran) to achieve target LDL cholesterol values [4].

ESC IIbC for alirocumab and evolocumab, RSC IIbC for inclisiran (LoE C, LoR 5)

3.3. Other treatment

• In patients with NSTE-ACS and blood glucose concentrations exceeding 10 mmol/L, it is recommended to use glucose-lowering medications to control glycemic levels [405-408].

ESC IIaC (LoE B, GoR 2)

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

To achieve target glycemic levels in patients with NSTE-ACS, an individualized approach to selecting glucose-lowering medications is recommended. The presence of type 2 diabetes mellitus in a patient with NSTE-ACS is not an absolute indication for switching to insulin therapy; many patients can continue taking oral glucose-lowering drugs. If a patient with type 2 diabetes mellitus requires insulin therapy, transitioning to oral glucose-lowering agents is recommended after stabilization of their condition.

Patients with NSTE-ACS who are without impaired consciousness or other serious complications and are capable of self-feeding may receive subcutaneous insulin therapy, provided it maintains glycemia within the target range and avoids hypoglycemia. The method of choice for rapid and controllable achievement of carbohydrate metabolism compensation is continuous intravenous infusion of rapid-acting insulins and analogs (Appendix A3. Intravenous Insulin Therapy in NSTE-ACS), combined with intravenous dextrose** infusion if necessary.

• In patients with NSTE-ACS without diabetes mellitus and with diabetes mellitus without glycemic control, simultaneous infusion of insulins and dextrose**, simultaneous infusion of insulins, dextrose**, and potassium chloride** is not recommended due to the lack of evidence of a positive effect on mortality and the incidence of nonfatal complications [4, 409].

ESC IIIC (CGR C, LOR 5)

• In patients with NSTE-ACS, non-steroidal anti-inflammatory and antirheumatic drugs are not recommended (with the exception of low-dose ASA** as an antiplatelet agent and moderate-dose ASA** for the treatment of pericarditis) due to their adverse effect on prognosis [410-411].

ESC IIIB (LOC A, LOE 1)

Comments: It is recommended to discontinue non-steroidal anti-inflammatory and antirheumatic drugs and/or avoid initiating their use upon hospitalization for NSTE-ACS.

• In patients with NSTE-ACS and anemia without signs of ongoing bleeding and hemodynamic instability, 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 potential adverse effects of blood transfusions on prognosis [4].

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

• In patients with NSTE-ACS who are in a coma after out-of-hospital or in-hospital cardiac arrest, targeted temperature management is recommended, including continuous core temperature monitoring and active prevention of fever (>37.7°C) for at least 72 hours to prevent complications [412-422].

ESC IB (LoE B, GoR 3)

• If pharmacological temperature control is not feasible in comatose patients with NSTE-ACS after cardiac arrest, the use of automated targeted temperature management systems utilizing special surface or endovascular devices with continuous feedback targeting 32–37°C should be considered, provided technical capabilities are available [412-422].

ESC IIaB (LOCE B, LOE 2)

3.4. Complications

3.4.1. Acute heart failure

Acute heart failure (AHF) can occur as a complication of NSTE-ACS or reflect the decompensation of pre-existing chronic heart failure (CHF) in the setting of ischemic myocardial injury. The development of AHF in patients with NSTE-ACS increases the risk of other complications: decreased 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 patients with NSTE-ACS. Early detection of impaired myocardial function via echocardiography allows for the timely initiation of therapeutic measures to prevent the development of heart failure.

The development of AHF in patients with NSTEMI worsens short-term and long-term prognosis. The Killip classification was developed and is used in patients with myocardial infarction (including NSTEMI) to assess the severity of AHF and evaluate short-term prognosis.

The main therapeutic strategy in patients with NSTE-ACS complicated by AHF is emergency myocardial revascularization to limit ischemic injury.

• In patients with NSTE-ACS and AHF, continuous monitoring of vital functions—at least heart rate, blood pressure, SpO₂, and urine output—is recommended until hemodynamic stabilization is achieved [4, 423, 424].

RSC IIaC (LOC C, LOE 5)

• In patients with NSTE-ACS presenting with signs of AHF, emergency echocardiography is recommended to assess LV systolic function, valvular status, and evaluate for mechanical complications [4].

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 systolic function and to identify/exclude mechanical complications of NSTEMI. Serial echocardiographic monitoring is also recommended to assess the efficacy and safety of ongoing therapy.

• To assess the presence and severity of AHF, the Killip classification is recommended in all cases of NSTEMI [4, 425, 426].

ESC IIaC (LoE C, GoR 5)

Comment: The Killip classification is provided 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, pulmonary capillary pressure increases, leading to the transudation of fluid from the intravascular space into the lung parenchyma. Interstitial and alveolar pulmonary edema are distinguished. Diagnosis of pulmonary edema is in most cases straightforward due to the typical clinical presentation. On examination, the most characteristic signs are: tachycardia, tachypnea, and an enforced elevated posture (orthopnea). Pulmonary auscultation reveals 'congestive' fine crackles. A decrease in blood oxygenation is recorded. The diagnosis can be confirmed using chest radiography and lung ultrasound. Patients with NSTE-ACS and AHF (especially with pulmonary edema) exhibit decreased blood oxygen saturation.

ESC IC (RR S, ELD 5)

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

Routine oxygen therapy in patients without hypoxemia (SpO₂ greater than or equal to 90%) is not recommended.

• To improve the efficacy of heart failure treatment in patients with NSTE-ACS with severe respiratory failure (SpO₂ below 90% and tachypnea above 25 breaths/min), it is recommended to consider non-invasive positive pressure ventilation via mask—either continuous or biphasic positive airway pressure (non-invasive ventilation, bilevel positive airway pressure ventilation) [427-429].

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). Creating positive airway pressure protects alveoli from expiratory collapse and maintains functional residual capacity in pulmonary edema. As a result, the work of breathing is reduced, pulmonary gas exchange is improved, and intrathoracic pressure increases, leading to a reduction in preload and afterload. Evidence suggests that non-invasive mask ventilation should be considered as soon as possible, as it reduces the likelihood of 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.

• In patients with NSTE-ACS presenting with respiratory failure accompanied by severe hypoxemia, hypercapnia, and acidosis, when oxygen therapy and non-invasive ventilation are ineffective, endotracheal intubation and invasive mechanical ventilation are recommended [427].

ESC I C (LoE C, LoR 5)

• In patients with NSTE-ACS and AHF with signs of fluid retention, intravenous administration of 'loop' diuretics is recommended [430, 431].

ESC I C (LoE C, GoR 5)

Comment: Intravenous bolus administration of furosemide** (group C03CA - sulfonamides) is used. The recommended initial dose is 40 mg. In florid alveolar pulmonary edema, signs of fluid retention, or severe renal filtration impairment, the initial dose of furosemide** may be increased to 60–80 mg. If the initial dose is insufficiently effective upon repeat administration, the dose of furosemide** may be doubled or increased further.

• In patients with NSTE-ACS and AHF with signs of fluid retention/congestion who do not respond adequately to escalating doses of loop diuretics, the combination of loop diuretics with thiazide diuretics (thiazides) should be considered to achieve stabilization [431].

ESC IIa B (LoE C, GoR 5)

• In patients with NSTE-ACS and AHF with signs of pulmonary congestion and a systolic blood pressure of 110 mm Hg or higher, and especially with markedly elevated blood pressure, intravenous infusion of vasodilators (group C01D - vasodilators used in cardiac diseases) should be considered to reduce AHF symptoms [432-436].

ESC IIb B (LoE C, LoR 5)

Comment: In patients with pulmonary edema and elevated blood pressure, nitroglycerin** is the first-line drug. If baseline systolic blood pressure is < 90 mm Hg or signs of hypoperfusion are present, as well as in right ventricular infarction, the administration of nitroglycerin is contraindicated.

• Routine administration of opioid analgesics in the development of AHF in patients with NSTE-ACS is not recommended except for patients with severe pain or agitation [437-440].

ESC III C (LoE C, LoR 4)

Comment: Retrospective analysis has shown that the use of opiates is associated with an increased need for mechanical ventilation, longer hospital stays, and increased in-hospital adverse outcomes.

3.4.1.2. Cardiogenic shock

Cardiogenic shock is the most severe form of AHF in patients with NSTE-ACS. Cardiogenic shock is a life-threatening condition caused by a sharp decrease in cardiac output and manifested by signs of profound organ and tissue hypoperfusion and tissue hypoxia, clinically presenting as cool, mottled skin, decreased urine output (< 40 mL/h), and altered mental status and consciousness.

There are 3 main pathogenetic variants of cardiogenic shock:

1. True cardiogenic shock, associated with decreased LV contractility.

2. Shock due to relative and absolute hypovolemia. A closely related variant is reflex shock associated with a reaction to a painful episode.

3. Arrhythmic variant—hemodynamic disturbances in the setting of severe tachy- and bradyarrhythmias (see section 'Arrhythmias').

According to the SHOCK registry, the causes of cardiogenic shock are distributed as follows: 79% have left ventricular systolic dysfunction, 7% acute mitral regurgitation, 4% ventricular septal rupture, 2% isolated right ventricular failure, 1.4% cardiac tamponade, and 7% other causes (catheterization complications, overdose or inappropriate use of beta-blockers, non-dihydropyridine calcium channel blockers, etc.) [290].

The primary clinical sign of cardiogenic shock is persistent hypotension (systolic BP ≤ 90 mm Hg) refractory to fluid resuscitation and accompanied by signs of acute multi-organ failure resulting from hypoperfusion. Today, objectifying hemodynamic parameters using invasive techniques, including Swan-Ganz catheterization, is not considered routinely mandatory, but it provides valuable data in controversial and complex cases.

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 during vasoactive therapy.

3. Increased filling pressures:

• Left ventricular end-diastolic pressure (LVEDP) > 18 mm Hg;

• Right ventricular end-diastolic pressure (RVEDP) > 10 mm Hg.

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

• In patients with NSTE-ACS and cardiogenic shock, central venous catheterization (subclavian and other central veins) is recommended for administering medications, primarily vasoactive drugs, and measuring mixed venous oxygen saturation and central venous pressure (CVP) (Appendix A3. Monitoring parameters in a patient with cardiogenic shock) [430, 442, 448].

RSC IIaC (LOC C, LOE 5)

• In patients with NSTE-ACS and cardiogenic shock, a clinical examination at least once an hour and monitoring of vital signs 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 [430, 442, 448].

RSC IIaC (LOC C, LOE 5)

Depending on clinical severity and response to treatment, the stages of cardiogenic shock include pre-shock, established 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).

Reperfusion therapy and myocardial revascularization form the basis of treatment for cardiogenic shock associated with NSTE-ACS.

Treatment of true cardiogenic shock

• Upon the appearance of signs of acute left ventricular failure / cardiogenic shock in patients with NSTE-ACS, emergency myocardial revascularization is recommended if it has not been previously performed or was incomplete [4, 137, 184].

ESC IA (Cochrane grade B, LEL 2)

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

• In patients with NSTE-ACS and cardiogenic shock, it is recommended to consider invasive central hemodynamic monitoring to control treatment efficacy and safety, as well as pulmonary artery catheterization to clarify the etiology of cardiogenic shock, provided physical and technical resources are available [4].

RSC IIaC (LOC C, LOE 5)

• In patients with NSTE-ACS and acute heart failure with a systolic BP below 90 mm Hg and signs of hypoperfusion, it is recommended to consider prescribing inotropic agents to correct hemodynamic instability [430, 441].

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 NSTE-ACS and acute heart failure who received chronic beta-blocker therapy prior to the onset of NSTE-ACS and in patients with inadequate urine output in response to repeated IV diuretic administration, levosimendan** (ATC 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 0.1 mcg/kg/min, titrated up to 0.2 mcg/kg/min (until systolic BP is stabilized for at least 3 hours). The recommended duration of infusion is 24 hours. In patients with systolic BP < 100 mm Hg and/or diastolic BP < 60 mm Hg, the initial levosimendan** bolus is typically omitted to prevent hypotension.

• In patients with NSTE-ACS and acute heart failure with a systolic BP under 90 mm Hg without signs of hypoperfusion, routine use of inotropic agents is not recommended, as potential benefits do not outweigh potential risks [441–443].

ESC III C (Cochrane grade C, LEL 4)

• In patients with NSTE-ACS and cardiogenic shock, to correct hemodynamic instability and maintain perfusion of vital organs during arterial hypotension, it is recommended to consider prescribing vasopressors, with norepinephrine** (IV infusion) preferred over dopamine** due to a lower incidence of adverse effects associated with norepinephrine** [444–446].

ESC IIb B (Cochrane grade A, LEL 2)

• In patients with NSTE-ACS and cardiogenic shock, if technically feasible, it is recommended to consider using temporary mechanical circulatory support devices: intra-aortic balloon pump, continuous-flow left atrial-to-aortic assist device, continuous-flow left ventricular-to-aortic assist device, pulsatile-flow left ventricular-to-aortic assist device, extracorporeal membrane oxygenation (ECMO) [4, 430, 447].

ESC IIaC (LoE C, GoR 5)

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

• In patients with NSTE-ACS and cardiogenic shock, it is recommended to consider intra-aortic balloon counterpulsation (IABC) if such treatment serves as a bridge to revascularization, heart transplantation, implantation of a durable mechanical circulatory support system, or another intermediate decision [448].

ESC IIbC (LoE C, GoR 5)

• Routine use of IABC in patients with NSTE-ACS and cardiogenic shock is not recommended unless this treatment serves as a bridge to another therapy for acute heart failure and/or its underlying cause [4, 449–452].

ESC III C (Cochrane grade C, LEL 5)

Management of hypovolemic cardiogenic shock

• All patients with NSTE-ACS and suspected hypovolemic shock are recommended to undergo echocardiography to identify potential causes of hypovolemia (right ventricular infarction, cardiac tamponade, etc.) and assess cardiac function [4, 453].

ESC IIb C (Cochrane grade C, LEL 5)

• In patients with NSTE-ACS and signs of hypovolemic shock, to ensure treatment efficacy and safety, it is recommended to monitor central hemodynamics, utilizing PCWP measurement via a Swan-Ganz catheter (standard pulmonary artery balloon catheter) if technically feasible [4, 453].

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

Comment: If PCWP measurement is unavailable, CVP may be assessed, but it should be noted that in patients with NSTE-ACS, CVP values may not reliably reflect LV end-diastolic pressure.

• In patients with NSTE-ACS and hypovolemic shock, fluid resuscitation to normalize blood pressure should be initiated with an IV infusion of 200–250 mL of 0.9% sodium chloride** solution administered over 5–10 minutes. If arterial hypotension persists, repeated administration of 0.9% sodium chloride** solution is recommended [4, 453].

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

Comment: The total volume of infused fluid may reach several liters. Infusion is stopped once blood pressure stabilizes and urine output resumes. If fluid administration is ineffective, concomitant therapy with adrenergic and dopaminergic agonists—dopamine** or dobutamine**—should be administered.

3.4.2. Cardiac rhythm and conduction disturbances

3.4.2.1. Ventricular arrhythmias

• In patients with NSTE-ACS complicated by hemodynamically significant ventricular tachycardia or ventricular fibrillation, immediate external electrical cardioversion (defibrillation) is recommended to restore circulation [4].

RSC IC (LoE C, GoR 5)

• In patients with NSTE-ACS and recurrent VT / VF, in order to eliminate ischemia as a possible cause of arrhythmias (if revascularization has not been performed previously or was incomplete), it is recommended to consider emergency and/or complete revascularization (see Invasive treatment of the disease) [4, 67, 454, 455].

ESC IC (RR S, ELD 5)

Comments: Complete revascularization is especially important in patients with NSTE-ACS with VT / VF in the presence of reduced global LV systolic function. If effective cardiac activity is absent, CPR and PCI may be performed concurrently with mechanical chest compressions using special devices — automated mechanical cardiopulmonary resuscitation devices.

• In NSTE-ACS patients with polymorphic VT or VF, in the absence of contraindications, intravenous administration of a beta-blocker and/or amiodarone is recommended** [322, 456-459].

ESC IB (LoE B, GoR 3)

Comment. Early intravenous administration of beta-blockers is not recommended in hypotension, cardiogenic shock, bradyarrhythmia, or suspected involvement of the right ventricular ischemia zone. Before starting beta-blockers, LV contractility should be assessed by echocardiography; in case of reduced LV contractility, it is advisable to use small doses or delay the initiation of therapy. When choosing a specific beta-blocker, its route of administration, and during dose titration, it is recommended to dynamically assess the patient's condition, therapy tolerance, achieved effect, and the presence of limiting factors: HR < 50 bpm, BP < 90 mmHg, LV EF value according to 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 NSTE-ACS patients with recurrent VT who are unresponsive to beta-blocker and amiodarone therapy** or in cases where these drugs cannot be prescribed, intravenous administration of lidocaine** is recommended to be considered [4, 322].

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

Comment: Lidocaine** – group C01BB – antiarrhythmic drugs, class IB.

• In NSTE-ACS patients with recurrent life-threatening VT unresponsive to beta-blocker or amiodarone therapy**, the possibility of sedation or general anesthesia to reduce sympathetic tone is recommended to be considered [67].

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

Comment: This method can be considered only in selected patients, as the risks of inflammatory and thrombotic complications may increase [67].

• In patients with NSTE-ACS who develop VT and/or VF, monitoring, identification, and correction of electrolyte disorders (primarily hypokalemia and hypomagnesemia) are recommended [4].

RSC IIaC (LOC C, LOE 5)

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

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

To correct hypokalemia, potassium chloride** can be administered intravenously; to correct magnesium levels, magnesium sulfate** is administered intravenously; the dose, regimen, and duration are determined individually, depending on blood electrolyte concentrations, acid-base balance parameters, and the clinical situation.

• In patients with NSTE-ACS with recurrent VT / VF and hemodynamic instability despite medical correction, it is recommended to consider mechanical circulatory support — if physical and technical capabilities are available [322].

ESC IIbC (LoE C, GoR 5)

• In patients with NSTE-ACS and VT and/or VF recurring despite revascularization and optimal medical therapy, it is recommended to perform radiofrequency ablation of arrhythmogenic zones in the subacute stage followed by ICD implantation [4].

ESC IIaC (LoE C, GoR 5)

• In patients with NSTE-ACS with sustained VT or VF occurring later than 48 hours from the onset of NSTE-ACS, in the absence of evidence of ongoing myocardial ischemia, ICD implantation is recommended — if technically feasible [322].

ESC IA (LoE C, SoR 5)

• In patients who have suffered an NSTEMI (at least 6 weeks ago) who, despite optimal medical therapy (for 3 months or more), have symptomatic chronic heart failure (NYHA class II-III) and LVEF ≤ 35%, with a life expectancy of at least 1 year and preserved functional status, recommendations include ICD implantation (combined with cardiac resynchronization therapy if indicated) [460, 461].

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

Comment: Criteria for determining life expectancy have not been developed. It is recommended to make the decision individually, taking into account the characteristics of each clinical case. A short life expectancy is indicated, in particular, by late-stage malignant neoplasms with metastases and no response to ongoing treatment, as well as palliative treatment of severe HF.

• In patients with polymorphic VT or VF occurring later than 48 hours from the onset of NSTE-MI, provided there is incomplete myocardial revascularization and a baseline low LVEF, it is recommended to consider ICD implantation or the use of a wearable cardioverter-defibrillator (WCD) within up to 40 days from the development of NSTE-MI [4].

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

• In patients with NSTE-ACS, treatment of asymptomatic and hemodynamically insignificant ventricular arrhythmias with antiarrhythmic drugs is not recommended [4, 322].

ESC IIIC (LoE C, GoR 5)

• In patients with NSTE-ACS, prophylactic prescription of antiarrhythmic drugs, with the exception of beta-blockers, is not recommended [322].

ESC IIIB (Level of Evidence C, Level of Evidence 5)

3.4.2.2. Atrial fibrillation

Atrial fibrillation (AF) is the most common type of supraventricular arrhythmia occurring in patients with NSTE-ACS. AF is generally well tolerated, but in some patients, tachy-arrhythmia can lead to hemodynamic instability. In hemodynamically stable patients, specific treatment is generally not required, with the exception of anticoagulant prophylaxis for thromboembolic complications.

• In patients with NSTE-ACS and newly onset AF with hemodynamic instability, immediate external electrical cardioversion is recommended [4].

ESC IC (LoE C, SoR 5)

• In hemodynamically unstable patients with NSTE-ACS and newly onset AF, intravenous amiodarone** is recommended to support external electrical cardioversion and reduce the risk of AF recurrence [4, 462, 463].

ESC IC (LoE C, GoR 5)

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

• In patients with NSTE-ACS and tachy-arrhythmic AF in the presence of acute heart failure, but in the absence of severe hypotension, intravenous amiodarone** is recommended for heart rate control [4, 292, 464].

ESC IC (LoE C, SoR 5)

Comments: Monitoring of the QT interval duration is necessary; if the QT interval duration exceeds 500 ms, amiodarone** administration is immediately discontinued.

• In patients with NSTE-ACS and AF in the absence of acute heart failure and hemodynamic instability (severe hypotension), intravenous beta-blockers are recommended if necessary for heart rate control [4, 465].

ESC IC (RR S, ELD 5)

• In patients with NSTE-ACS and AF first occurring in the acute phase of the disease, it is recommended to consider prescribing oral anticoagulants indefinitely, with a reassessment of the entire antithrombotic therapy depending on the risk of thromboembolic complications according to the CHA₂DS₂-VASc score and bleeding risk according to the HAS-BLED score [4, 466-468].

ESC IIaC (LoE C, GoR 5)

Comments: The need to adjust the timing of dual antiplatelet therapy and single antiplatelet monotherapy as part of antithrombotic therapy in patients with NSTE-ACS and AF is determined by the balance of thromboembolic, ischemic, and hemorrhagic risks and is presented 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 NSTE-ACS who develop hemodynamically significant sinus bradycardia or hemodynamically significant AV block (with an inadequate escape rhythm) to stabilize hemodynamics, intravenous administration of drugs with a positive chronotropic effect (epinephrine**, atropine**) is recommended [4, 469, 470].

ESC IC (RR S, ELD 5)

Comment: At a heart rate of 40 bpm and/or pauses of more than 300 ms, atropine** 0.6-1.0 mg is administered. Epinephrine** – group C01CA – adrenergic and dopaminergic agents. If marked bradycardia persists, a pacemaker is implanted.

• In patients with NSTE-ACS and a hemodynamically significant AV block (with an inadequate replacement rhythm) when atropine is ineffective, temporary endocardial pacing is recommended to stabilize the patient's condition, provided physical and technical capabilities are available [4].

ESC IC (RR S, ELD 5)

• In patients with NSTE-ACS who develop hemodynamically significant sinus bradycardia or a hemodynamically significant AV block (with an inadequate replacement rhythm) when prior revascularization has not been performed or was incomplete, urgent coronary angiography with the intention to perform PCI, including complete revascularization, is recommended [4].

ESC IC (RR S, ELD 5)

• In patients with NSTE-ACS who have general population indications for permanent pacemaker implantation, the permanent pacemaker implantation procedure is recommended; in patients with NSTEMI, this should be done no earlier than 5 days after its onset [4, 471].

ESC IC (RR S, ELD 5)

Comment: The question of permanent pacemaker implantation should be addressed on days 10–14 from the onset of NSTEMI. Earlier implantation (starting from the 5th day from disease onset) is advisable in patients with hemodynamically significant bradycardia and late and/or incomplete revascularization in anterior NSTEMI, in the presence of a bifascicular block; if AV block was present before the onset of NSTEMI; and with progression of the degree of AV block during the first day of the disease.

• In selected patients with anterior NSTEMI, high-degree AV block, and severe heart failure, early initiation of cardiac resynchronization therapy is recommended if technically feasible [4, 448].

ESC IIbC (LoE C, GoR 5)

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

ESC IIIB (LoE C, GoR 5)

3.4.3. Mechanical complications

Mechanical complications of MI—free wall rupture, interventricular septum rupture, and acute mitral regurgitation due to ischemic damage to the valvular structures—are life-threatening conditions that occur with a frequency of less than 0.1% of patients with NSTE-ACS in the reperfusion era.

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 NSTEMI presenting with mechanical complications and hemodynamic instability, the use of an IABP*** system and/or other mechanical circulatory support devices is recommended as a temporary measure to stabilize the condition prior to surgical intervention [4, 474–477].

ESC IIaC (LoE C, GoR 5)

Left ventricular free wall rupture

• In cases of proven LV free wall rupture in a patient with NSTEMI leading to cardiac tamponade or worsening signs thereof, immediate pericardiocentesis followed by emergency surgery is recommended [4, 474–477].

RSC IIaC (LOC C, LOE 5)

Ventricular septal rupture

• In patients with NSTEMI who develop an interventricular septum rupture, surgical treatment (closure of the septal defect) is recommended to prevent a fatal outcome [4, 474–477].

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 reconstruction of the interventricular septum is preferable after stabilization; however, in cases of severe hemodynamic compromise, emergency surgery is performed.

Acute mitral regurgitation

Acute mitral regurgitation in NSTE-ACS may result from ischemia and papillary muscle dysfunction. In NSTEMI, it typically develops on days 2–7 due to rupture of a papillary muscle or chordae. Rupture can be complete or involve only individual muscle heads. Rupture of the posteromedial muscle occurs most frequently due to its specific blood supply features. In some cases, severe mitral regurgitation develops in patients with NSTE-ACS without rupture or infarction of the papillary muscle as a consequence of extensive LV damage with subsequent dilatation and expansion of the mitral annulus. Clinically, acute mitral regurgitation manifests as acute heart failure, pulmonary edema, and sometimes cardiogenic shock. The diagnosis is confirmed by echocardiography.

• In patients with NSTEMI who develop acute mitral regurgitation, surgical treatment—typically mitral valve replacement (mitral valve replacement under cardiopulmonary bypass; mitral valve repair under cardiopulmonary bypass; reconstruction of mitral subvalvular structures)—is recommended to resolve acute heart failure and prevent death. The timing of the intervention depends on the degree of mitral regurgitation and the patient's condition. In most cases, surgery is performed on an emergency basis [4, 475, 476, 478, 479].

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, surgery is performed on an emergency basis.

• In patients with NSTEMI who develop acute mitral regurgitation, the use of an IABP system and/or other mechanical circulatory support devices is recommended as a temporary measure to stabilize the condition [4, 475, 476].

ESC IIbC (LoE C, GoR 5)

3.4.4. Pericarditis

Pericarditis may complicate the early period of NSTEMI (from several hours to 4 days) and usually resolves quickly on its own (early post-infarction pericarditis, syn.: epistenocarditic pericarditis) or develop in a later period (1–2 weeks later, sometimes symptoms may last for several weeks)—late post-infarction pericarditis, syn.: Dressler's syndrome. As a rule, the likelihood of developing pericarditis is directly dependent on the extent of myocardial damage and has no independent prognostic significance. Classical Dressler's syndrome presenting as full-blown 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 patients with NSTEMI and early post-infarction pericarditis with pronounced clinical manifestations, the use of #ASA** at a dose of 500 mg every 8–12 hours is recommended as anti-inflammatory therapy [4, 480, 481].

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 patients with NSTEMI and late post-infarction pericarditis with 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 dose reduction of 250–500 mg every 2 weeks is recommended as anti-inflammatory therapy [4, 480, 481].

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 a body weight ≥ 70 kg) or 0.5 mg once daily (in patients with a body weight < 70 kg) [4, 480, 481].

RSC IIaC (LOC C, LOE 5)

3.4.5. Acute left ventricular aneurysm and left ventricular thrombosis

Acute left ventricular aneurysm usually develops with extensive anterior NSTEMI, 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.

Mural thrombosis in the LV cavity is found in almost all cardiac aneurysms in at least half of cases of extensive anterior NSTEMIs. In the population of patients with widespread anterior STEMI, LV thrombosis occurs in more than 9% of cases. The diagnostic methods for acute LV aneurysm and LV mural thrombosis are echocardiography.

• In patients with NSTEMI with a high clinical probability of an LV thrombus but equivocal echocardiographic results, cardiac MRI is recommended to confirm or exclude an LV thrombus, provided physical and technical capabilities are available [4, 90].

ESC IIaC (LoE C, GoR 5)

• In patients with anterior NSTEMI with unclear visualization of an LV thrombus on routine transthoracic echocardiography, the option of contrast-enhanced echocardiography is recommended to be considered to confirm or exclude an LV thrombus, provided physical and technical capabilities are available [482].

ESC IIbC (LoE C, GoR 4)

Comment: Contrast echocardiography is currently at the stage of introduction into clinical practice in the Russian Federation.

• In the presence of an LV thrombus in patients with NSTEMI, the prescription of oral anticoagulants (vitamin K antagonists or direct oral anticoagulants (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban)) for 3–6 months is recommended [4, 483].

ESC IIaC (LoE C, GoR 5)

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

The traditional therapy for a left ventricular cavity thrombus is a vitamin K antagonist monitored by INR (target range 2.0–3.0); during the titration period of the vitamin K antagonist, administration of a therapeutic dose of a parenteral anticoagulant should be continued. The use of direct oral anticoagulants is not excluded, but has been little studied so far.

3.4.6. Early post-infarction angina and recurrent myocardial infarction

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 patients with NSTE-ACS presenting with an anginal attack lasting more than 20 minutes to diagnose recurrent myocardial infarction, it is recommended to measure cardiac troponin I or T levels with re-evaluation after 6 hours. An increase in cardiac troponin by 20% or more from the baseline level combined with criteria for myocardial ischemia indicates recurrent myocardial infarction [10].

ESC IIaC (LoE C, GoR 5)

• To prevent the expansion of the myocardial infarction zone in patients with NSTE-ACS and early post-infarction angina and/or recurrent myocardial infarction, it is recommended to perform coronary angiography and, if necessary, revascularization [4, 137].

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

3.5. Right ventricular NSTEMI

Isolated right ventricular myocardial infarction is rare; it is most commonly observed in combination with inferior left ventricular myocardial infarction. Clinically, right ventricular myocardial infarction is characterized by arterial hypotension, jugular venous distension in the absence of signs of pulmonary congestion. Hypotension in right ventricular myocardial infarction is associated with relative hypovolemia.

• In patients with inferior NSTE-ACS, to rule out or detect right ventricular involvement in the zone of myocardial necrosis, 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 myocardial infarction) and perform an echocardiogram to search for right ventricular regional wall motion abnormalities and cavity dilatation [4, 63].

ESC IIaC (LoE C, GoR 5)

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

• In patients with NSTE-ACS involving the right ventricle, to eliminate hypotension, it is recommended to increase the volume of blood returning to the right heart chambers by administering plasma expanders (e.g., sodium chloride** 0.9% solution). In more severe cases, adrenergic and dopaminergic agents (group C01CA — adrenergic and dopaminergic agents) are recommended [4].

ESC IIaC (LoE C, GoR 5)

• In NSTE-ACS involving the right ventricle, due to the risk of worsening relative hypovolemia, it is recommended to avoid prescribing diuretics and, especially, peripheral vasodilators [4, 18].

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

3.6. Treatment of elderly and senile patients

• In elderly and senile patients with NSTE-ACS, it is recommended to use the same diagnostic and treatment strategies as in younger patients to improve their clinical status and prognosis [484, 485].

ESC IB (LoE A, GoR 2)

Comment: Impairment of organ and system function 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 NSTE-ACS treatment and worsen the prognosis of such patients both during hospitalization and after discharge [387, 486-489].

• To increase the safety of antithrombotic agents and secondary prevention drugs in elderly and senile patients with NSTE-ACS, the selection and doses of these medications should be adapted taking into account renal filtration function, comorbidities, presence of geriatric syndromes (frailty, falls, cognitive impairment, polypharmacy, etc.), and specific drug contraindications [484, 485, 490, 491].

ESC IB (LoE A, GoR 2)

Comment: In elderly and senile patients with STEMI during hospitalization, it is advisable to assess for the presence of geriatric syndromes and implement preventive measures 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 systems.

Ideally, the management of elderly and senile patients with NSTE-ACS should be carried out by a multidisciplinary team including a geriatrician or cardiologist trained in geriatrics, starting from their stay in the intensive care unit [492, 493].

Screening, prevention, and correction of geriatric syndromes in elderly and senile patients with NSTE-ACS 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 [494, 495].

• To increase treatment safety in every NSTE-ACS patient with frailty syndrome and significant comorbidities, it is recommended to take an individualized approach to the choice and scope of interventional and pharmacological treatment with a thorough comprehensive assessment of all risks and benefits [484, 485, 496-498].

ESC IB (LoE A, GoR 2)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• All patients who have undergone NSTE-ACS are recommended to undergo cardiac rehabilitation (CR) to reduce the risk of death and hospitalization rates, improve prognosis, quality of life and psychosocial status, increase physical performance, restore cardiovascular system functions, promote a healthy lifestyle, correct cardiovascular risk factors, and increase treatment adherence [499-503].

ESC IA (LoE A, GoR 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 outpatient settings [504].

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 had 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 [504].

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 who have undergone NSTE-ACS, the outpatient stage of CR is recommended to be carried out in-person, remotely (at home using digital and mobile health tools), or in a blended format to increase patient coverage by rehabilitation and enhance their adherence to CR and treatment as a whole [505-509].

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

• To implement the CR program in patients who have undergone NSTE-ACS, it is recommended to form a multidisciplinary rehabilitation team at all stages to assess the patient's clinical and functional status, determine and carry out a set of rehabilitation measures [499, 504, 510, 511].

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) [512, 513].

• All patients after NSTE-ACS are recommended to undergo an exercise tolerance test (exercise testing using a cycle ergometer or treadmill) or cardiopulmonary exercise testing (quantitative assessment of oxygen consumption during ergospirometry)—if available and the institution has sufficient experience in performing it; if these are unavailable (or contraindicated), a 6-minute walk test is recommended to assess functional status, exercise tolerance, select the optimal exercise training regimen, and monitor their efficacy and safety [514, 515].

ESC IA (LoE C, GoR 5)

Comment: Exercise testing is performed before starting the exercise training program and after completing the cardiac rehabilitation phase.

• All patients after NSTE-ACS are recommended to undergo moderate-intensity aerobic exercise training (exercise therapy using exercise machines for heart and pericardial diseases; individual exercise therapy sessions for heart and pericardial diseases; group exercise therapy sessions for heart and pericardial diseases; exercise therapy with biofeedback for heart and pericardial diseases) to improve functional status, reduce symptoms, increase physical performance, improve quality of life, and reduce the risk of cardiovascular events, hospitalization rates, and mortality [499, 503, 511, 516-519].

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

Comment. In patients after NSTE-ACS, it is recommended to rule out contraindications before prescribing exercise training (Appendix A3. Main contraindications to exercise training) [515, 520]. During the early phase 1 of cardiac rehabilitation, a stepwise expansion of physical activity and the use of exercise complexes are recommended. At later phases (2 and 3), the cardiac rehabilitation program should include exercise training in an individual format and/or in organized groups at a medical facility and/or at home after education [521].

The recommended duration of dynamic exercise 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); training intensity is moderate (55-69% of maximum heart rate during exercise testing or in the 12-14/20 score zone 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 [499, 517, 520, 522, 523].

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 evaluate the level of physical exertion using the Borg scale during the training session [523].

Patients after NSTE-ACS 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 after completing cardiac rehabilitation programs. 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 condition.

• In selected patients after NSTE-ACS with a low risk of complications (including atherothrombotic and ischemic risks) and upon their preference, it is recommended to consider high-intensity interval training to improve physical performance and quality of life [524-526].

ESC IIb C (LoE A, GoR 1)

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

• Patients after NSTE-ACS are recommended to undergo an assessment of 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 [527-529].

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

Comment: In the presence of clinically pronounced anxiety and/or depressive symptoms, psychological counseling and support, and psychopharmacotherapy (as indicated) are recommended, which, combined with structured education and exercise training, can reduce depression symptoms, improve social functioning, cognitive profile, and the patient's quality of life [197, 528, 530-533].

• All patients after NSTE-ACS are recommended to complete an educational program in any available format (individually and/or in groups—"School for Patients after ACS" 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 improve adherence to treatment and rehabilitation interventions [534, 535].

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 can be conducted in a remote support format).

5. Prevention and Dispensary Observation

5.1. Prevention

In addition to continuing pharmacotherapy initiated in the early stages of NSTE-ACS treatment (Section 3.1), interventions to control cardiovascular risk factors and prevent sudden cardiac death are recommended (Section 3.3.2.1).

• To reduce the risk of cardiovascular events among patients after NSTE-ACS, it is recommended to identify smokers and implement regular interventions aimed at complete smoking cessation, including avoidance of passive smoking [536-549].

ESC IIaA (LOE A, GoE 1)

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

• To reduce the risk of adverse outcomes, patients after NSTE-ACS are recommended to adhere to healthy eating principles, maintain a normal body weight, engage in regular physical exercise, and limit alcohol intake [4, 499, 550-565].

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

Comments: Key characteristics of a healthy diet: limiting the intake of saturated fats and trans-fatty acid isomers to < 10% and < 1% of total daily calorie intake, respectively; table salt to < 5 g per day; easily digestible carbohydrates; consuming large amounts of fruits (≥ 250 g per day), vegetables (≥ 250 g per day), and whole-grain products. Consumption of fish 1–2 times a week (at least once a week for fatty fish), as well as low-fat dairy products, lean meat and poultry, legumes, and unsalted nuts in the amount of 30 g per day, is recommended.

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 after NSTE-ACS, to reduce the risk of ischemic events and death, blood pressure control and maintenance at the target level are recommended [353, 361, 566-569].

ESC IA (LoE A, GoR 1)

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

• In patients with diabetes mellitus who have suffered NSTE-ACS, it is recommended to administer treatment aimed at maintaining the individual target glycated hemoglobin level chosen in agreement with an endocrinologist (below 7.0% in most patients) to reduce the risk of micro- and macrovascular complications of diabetes mellitus [570-573].

ESC IIa B (CARR B, LER 2)

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

• Annual influenza vaccination is recommended for patients after NSTE-ACS to reduce the risk of cardiovascular complications and death [574-582].

ESC IA (LoE A, GoR 2)

• In cases of inadequate risk factor control or the occurrence of cardiovascular complications despite optimal pharmacotherapy in patients after NSTE-ACS, it is recommended to consider the use of low doses (0.5 mg/day) of #Colchicum autumnale seed extract (colchicine) [583, 584].

ESC IIbA (LoE A, GoR 2)

• In patients after NSTE-ACS, fixed-dose combinations of drugs are recommended to improve treatment adherence and reduce the risk of adverse outcomes [585-587].

ESC IIa B (LoE B, GoR 2)

5.2. Dispensary follow-up

• Upon discharge from the hospital, a patient who has suffered NSTE-ACS (NSTEMI or UA) must be provided with oral and written information regarding their condition [588, 589].

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

ESC IC (LoE C, GoR 5)

ESC IC (LoE C, GoR 5)

Comments: 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 conducting regular clinical follow-up of adults", follow-up of patients in the first 12 months after MI, PCI, or CABG is carried out by a cardiologist. Patients with UA are not mentioned in this Order. However, due to the poor prognosis after an episode of UA, such patients also need follow-up by a cardiologist, even if they did not undergo PCI or CABG.

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, heart rate, determine body weight (with calculation of body mass index), measure waist circumference, and assess smoking status [591].

• In patients with a history of NSTE-ACS (NSTEMI or UA), to assess lipid metabolism disorders and monitor the efficacy of lipid-خفض-therapy (lipid-lowering therapy), it is recommended to perform a biochemical blood test to evaluate lipid metabolism disorders (at least testing LDL-C levels) at least twice a year [591].

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 with a history of NSTE-ACS (NSTEMI or UA), it is recommended to perform a complete blood count (CBC) and general biochemical blood panel (with eGFR calculation) at least once a year to monitor treatment safety and timely adjust therapy [591].

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 with a history of NSTE-ACS (NSTEMI or UA) taking vitamin K antagonists, determination of INR is recommended at least twice a year to monitor treatment efficacy and safety, as well as to select the drug dose [591].

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 with a history of NSTE-ACS (NSTEMI or UA), ECG recording is recommended at least once a year to detect signs of disease progression, cardiac arrhythmias and conduction disturbances, as well as for timely therapy adjustment [591].

ESC IC (LoE C, GoR 5)

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

• In patients with a history of NSTE-ACS (NSTEMI or UA), chest X-ray is recommended at least once a year to detect signs of pulmonary congestion [591].

ESC IC (LoE C, GoR 5)

• In patients with a history of NSTE-ACS (NSTEMI or UA), echocardiography with mandatory assessment of LVEF is recommended at least once a year to monitor the dynamics of changes associated with the prior ACS, detect new pathological findings, and timely adjust therapy [591].

ESC IC (LoE C, GoR 5)

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

• In patients with a history of NSTE-ACS (NSTEMI or UA) who have undergone PCI or CABG, performing a non-invasive stress test (see Terms and Definitions) is recommended at least once every 2 years to detect myocardial ischemia and/or assess its severity [591].

Comments: Non-invasive stress tests may be performed in all patients with a history of NSTE-ACS (NSTEMI or UA) in accordance with clinical necessity.

ESC IC (LoE C, GoR 5)

6. Organization of Medical Care

6.1. Indications for hospitalization

Any suspicion of NSTE-ACS is an indication for emergency hospitalization.

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

• At the pre-hospital stage, instrumental/laboratory diagnostic measures, with the exception of ECG, aimed at confirming or ruling out NSTE-ACS (NSTEMI or UA) are not recommended [4, 242, 243, 592-595].

ESC IC (RR S, ELD 5)

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

• If NSTE-ACS 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 [4].

ESC IC (RR S, ELD 5)

• In each region, it is recommended to develop a regional routing protocol for patients with NSTE-ACS, taking into account current guidelines and regional characteristics [4].

ESC IC (RR S, ELD 5)

• In each region, it is recommended to designate a specialized cardiac surgery department for emergency CABG procedures in ACS patients, as well as to develop regional rules for the emergency transfer of such patients [4].

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 ruling out the diagnosis of NSTE-ACS (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 with NSTE-ACS are recommended for discharge provided clinical stabilization has been achieved, risk stratification for adverse outcomes is complete (including coronary angiography and/or non-invasive stress tests where indicated), and the chosen treatment strategy has been implemented. Once the preliminary diagnosis of NSTE-ACS is confirmed, a final clinical diagnosis must be formulated – NSTEMI or UA.

The safety of early discharge (48–96 hours) after PCI is determined primarily by the absence of early complications such as recurrent ischemia, stent thrombosis, acute heart failure, supraventricular and ventricular arrhythmias, conduction disturbances, rupture of the interventricular septum or LV free wall, acute mitral regurgitation, pericarditis, and LV 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.

• Early discharge of patients with NSTE-ACS after PCI is recommended in selected patients, provided early rehabilitation and adequate follow-up are organized [258, 272, 500].

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

Comment: In the case of early discharge during hospitalization, the patient must start rehabilitation, 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

If NSTE-ACS is suspected, intensive monitoring of patients in the intensive care unit (ward) with continuous electrocardiographic monitoring (ECG monitoring) is recommended to control heart rhythm until the presence of NSTE-ACS is confirmed or ruled out, the risk of adverse outcomes is determined, the management strategy is chosen, and other life-threatening diseases and complications are excluded.

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

Remote electrocardiographic monitoring (ECG monitoring) for heart rhythm control is recommended to be extended in patients at high risk for arrhythmias (hemodynamic instability, history of serious arrhythmias, LVEF ≤ 40%, unsuccessful reperfusion therapy, persistent critical stenoses in major coronary arteries, PCI complications, GRACE risk score > 140). In patients without signs of ongoing myocardial ischemia, extension of remote electrocardiographic monitoring (ECG monitoring) for heart rhythm control may be considered if coronary artery spasm is suspected or if symptoms are present that do not allow arrhythmia to be ruled out.

7. Additional Information

Additional information is provided in Appendices A3 and B1-B3.

Criteria for Evaluating the Quality of Medical Care

Criteria for assessing the quality of primary health care provided to adults with acute non-ST-segment elevation myocardial infarction (ICD-10 codes: I20.0, I21.0, I21.1, I21.2, I21.3, I21.4, I21.9, I22.0, I22.1, I22.8, I22.9, I24.8, I24.9)

Criteria for assessing the quality of specialized medical care provided to adults with acute non-ST-segment elevation myocardial infarction (ICD-10 codes: I20.0, I21.0, I21.1, I21.2, I21.3, I21.4, I21.9, I22.0, I22.1, I22.8, I22.9, I24.8, I24.9)

References

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 A.N. (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)

All members of the Working Group have confirmed that they have no financial support or conflicts of interest to disclose. In the event of a reported conflict of interest, working group members were excluded from discussions related to the area of conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

The recommendations are based on the results of large-scale multicenter studies, meta-analyses, and registries, which also serve as the foundation for other national and international clinical guidelines. They take into account 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 for myocardial revascularization, dual antiplatelet therapy, and chronic coronary syndromes, as well as the joint recommendations of these professional societies on antithrombotic therapy in patients with AF. At the same time, differences and specific features of medical care delivery for patients with ACS in the Russian Federation were taken into consideration.

Target audience for these clinical guidelines:

1. Cardiologist,

2. Critical care physician / Anesthesiologist-resuscitologist,

3. Ambulance paramedic,

4. Ambulance physician,

5. General physician / Internist,

6. General practitioner / District internist,

7. General practitioner (family physician),

8. Cardiovascular surgeon,

9. Endovascular Surgeon.

European Society of Cardiology (ESC) Class of Recommendation Scale

Because members of the Russian Society of Cardiology (RSC) are also members of the European Society of Cardiology, 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. Consequently, the National Guidelines were developed based on the ESC guidelines, taking into account national specifics, diagnostic and treatment characteristics, and the availability of medical care. For this reason, the text of these clinical guidelines simultaneously employs two scales for assessing the certainty of evidence for recommendation statements: the ESC levels of evidence combined with levels of evidence certainty (LEC) and levels of evidence validity (LEV). ESC recommendation classes have also been added to assess the necessity of performing a recommendation statement (Tables 1, 2, 3, 4, 5).

Table 1. Classes of recommendations according to the European Society of Cardiology (ESC) guidelines

Table 2. Levels of evidence certainty according to the European Society of Cardiology (ESC) guidelines

Table 3. Scale for assessing the levels of evidence certainty (LEC) for diagnostic methods (diagnostic interventions)

Table 4. Scale for assessing the levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

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

Procedure for updating clinical guidelines

The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

The decision to update is made by the Russian Ministry of Health based on proposals submitted by medical non-profit professional organizations. The formulated proposals must take into account the results of comprehensive assessments of medicinal products and medical devices, as well as the results of clinical testing.

Appendix A3. Reference Materials

1. 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).

2. Order of the Russian Ministry of Health No. 158n dated March 2, 2021, "On Approval of the Standard of Medical Care for Adults with Acute Coronary Syndrome Without ST-Segment Elevation on Electrocardiography (Diagnosis, Treatment, and Dispensary Follow-up)."

3. 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."

4. "Methodological Recommendations for Assessing the Scientific Validity of Information Included in Clinical Guidelines," Center for Expertise and Quality of Medical Care of the Russian Ministry of Health, 2019.

Diagnostic criteria for myocardial infarction

Presented according to the Fourth Universal Definition of MI [10].

Diagnostic criteria for acute MI

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 rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit (URL) in patients with a baseline normal cardiac troponin level, or a rise > 20% if the baseline cardiac troponin values are elevated and are stable (variation ≤ 20%) or falling, combined with at least one of the criteria for acute myocardial ischemia.

Symptoms of myocardial ischemia:

• New or presumed new significant ischemic ECG changes;

• Development of pathological Q waves on the ECG;

• Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality consistent with an ischemic etiology;

• Identification of a coronary thrombus by coronary angiography or intracoronary imaging, or identification of atherothrombus (or signs of an unstable atherosclerotic plaque) at autopsy (for Type 1 MI).

Criteria for differential diagnosis of Type 1 and Type 2 MI are presented in Fig. 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 rise in cardiac troponin concentration greater than 5 times the 99th percentile upper reference limit in patients with a normal baseline level (if pre-procedural troponin concentrations were elevated and stable (variation ≤ 20%) or falling, the post-procedural value must rise by > 20%) combined with at least one of the following evidence of acute myocardial ischemia:

• New ischemic ECG changes;

• Development 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 vessel or side branch, disruption of collateral flow, or distal embolization;

• Post-mortem demonstration of a procedural-related thrombus in the target artery or a myocardial necrosis area supplied by that artery.

Diagnostic criteria for type 4b acute MI

Criteria for acute Type 1 MI in combination with coronary 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 rise in cardiac troponin concentration greater than 10 times the 99th percentile upper reference limit in patients with a normal baseline level (if pre-procedural troponin concentrations were elevated and stable (variation ≤ 20%) or falling, the post-procedural value must rise by > 20%) combined with at least one of the following evidence of acute myocardial ischemia:

• Development 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 occlusion of a bypass graft or native coronary artery documented by coronary angiography.

Biochemical diagnosis of acute MI should rely on cardiac troponin assays with a coefficient of variation (CV) at the 99th percentile upper reference limit of ≤ 20% (optimally ≤ 10%).

Figure 3. Diagnosis and differential diagnosis of acute Type 1 and Type 2 MI [10].

Diagnostic criteria for prior MI

• Pathological Q waves on the ECG with or without symptoms, in the absence of non-ischemic causes.

• Imaging evidence of a region of loss of viability with a pattern consistent with an ischemic etiology;

• Morphological findings characteristic of a healed MI.

Causes of elevated cardiac troponin concentrations

Note. Presented according to the Fourth Universal Definition of MI [10].

Algorithm for ruling out and ruling in acute myocardial injury based on blood cardiac troponin levels determined by high-sensitivity methods at admission and after 1 or 2 hours

Notes. Laboratory methods for determination using reagents from various manufacturers validated within this protocol are presented [31-48]. If neither ruling in nor ruling out MI is possible after two determinations of blood cardiac troponin levels using a high-sensitivity method at an interval of 1 h or 2 h, and clinical suspicion of ACS persists, an additional determination after 3 h is recommended. This algorithm allows the detection of acute myocardial injury regardless of its cause. Diagnosis of acute MI requires the presence of criteria corresponding to the Fourth Universal Definition of MI (Appendix A3. Diagnostic criteria for myocardial infarction) [10].

Algorithm for ruling out and ruling in acute myocardial injury based on blood cardiac troponin levels determined by high-sensitivity methods at admission and after 3 hours

Notes. * 99th percentile of the upper reference limit for the given assay method; ** the magnitude of change depends on the cardiac troponin assay method [31-48].

ECG changes affecting the management of a patient with NSTE-ACS

ECG changes in patients with NSTE-ACS indicating occlusive coronary artery disease [4]

Notes: PDA – posterior descending artery, MI – myocardial infarction, LV – left ventricle, LMCA – left main coronary artery, LCx – circumflex artery, RCA – right coronary artery, LAD – left anterior descending artery.

Risk categories for adverse outcomes in NSTE-ACS

Medical treatment of NSTE-ACS

Notes.

The table presents medications most extensively studied in acute coronary syndrome. The use of other drugs with a similar mechanism of action is not excluded.

Within each group, drugs are listed in alphabetical order.

^ Other drugs at appropriate doses that do not possess intrinsic sympathomimetic activity may also be used.

^^ In each specific case, beta-blocker doses may be lower or somewhat higher depending on individual tolerance and clinical response in the particular patient; in patients with chronic heart failure and significantly impaired LV systolic function, a beneficial effect on survival 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** at a target dose of 200 mg once daily.

^^^ In patients with myocardial infarction and significantly impaired LV systolic function (EF ≤ 40%), a favorable effect on mortality has been demonstrated.

^§ Drugs with a proven positive effect on post-infarction mortality are indicated; specific dose titration features in an individual patient depend on blood pressure response, blood creatinine, and potassium levels; if the target dose of the drug cannot be achieved, the maximum tolerated dose should be used.

^& Evidence of a positive effect on prognosis has been obtained in patients with heart failure (including transient heart failure in the early stages of MI) and/or LVEF < 40%.

^&& Evidence of a positive effect on prognosis has been obtained in patients without a marked decrease in LV contractility.

^&&& If eplerenone is unavailable, #spironolactone** can be used in the same doses [112, 622].

Doses of antithrombotic drugs in renal impairment

Notes. CrCl — creatinine clearance;

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

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

Intravenous insulin therapy in NSTE-ACS

Indications for insulin therapy in patients with NSTE-ACS and DM

• Type 1 diabetes mellitus

• Plasma glucose level upon admission and on subsequent determinations persistently above 10 mmol/L

• Diabetic ketoacidosis

• Hyperosmolar hyperglycemic state

• Known treatment with high-dose glucocorticoids

• Parenteral nutrition

• Severe/critical condition

• Cardiogenic shock, severe 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 infusion of insulins is performed via a dedicated syringe pump using a solution of rapid-acting insulins and analogues 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 blood 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. Critical care patients require blood plasma glucose determination once an hour even at a stable target level.

• The recommended average initial rate of continuous intravenous insulin infusion in patients already having blood plasma glucose levels within the target range is 0.5–1 IU/h; for those not in 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 initial rate (< 0.5 IU/h) is used in underweight patients, renal, hepatic, or adrenal failure. A higher initial rate (> 3 IU/h) is used in ultra-high hyperglycemia (> 25 mmol/L) and suspected insulin resistance (pronounced obesity, signs of infection, chronic glucocorticoid therapy).

• Simultaneously with continuous intravenous insulin infusion, it is advisable to set up an infusion of a 5–10% dextrose** solution (administering 5 g of dextrose** 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. At blood plasma glucose levels above 14 mmol/L, dextrose** is not administered (until the next glucose determination).

• At blood plasma glucose levels below 3.3 mmol/L, it is necessary to stop the insulin infusion and administer 30–60 mL of 40% dextrose** solution intravenously, repeating the 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, insulin infusion is stopped 1–2 hours after the first subcutaneous injection of rapid-acting insulins and analogues, or 2–3 hours after the first injection of long-acting insulins and analogues.

Recommended insulin infusion rate according to blood plasma glucose level.

Individual patients (previously receiving > 80 IU of insulin per day, receiving glucocorticosteroids, failing to achieve target glycemia using the proposed algorithm) may require more intensive algorithms. Patients with repeated blood plasma glucose determinations below 3.9 mmol/L (two consecutive times) must be switched to a less intensive algorithm. These algorithms can be found in the guidelines for the management of patients with DM.

Classification of acute heart failure in myocardial infarction according to Killip [425, 426]

Hemodynamic variants of cardiogenic shock

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

Parameters to monitor in a patient with cardiogenic shock

Notes. BP — blood pressure, ALT — alanine aminotransferase, AST — aspartate aminotransferase, IMV — invasive mechanical ventilation, LDH — lactate dehydrogenase, UFH — unfractionated heparin sodium**, CVP — central venous pressure.

Stages of cardiogenic shock according to clinical severity and response to treatment

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

Notes. Adapted from [596]; MI — myocardial infarction, ECMO — extracorporeal membrane oxygenation.

Main contraindications to physical training

Main contraindications to physical training

- ACS;

- 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 (sinoatrial and 2nd–3rd degree AV blocks, except in patients with implanted pacemakers);

- uncontrolled hypertension (> 180/110 mm Hg; decrease in systolic BP ≥ 20 mm Hg 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. Selection of management strategy for patients with NSTE-ACS

Appendix B2. Prehospital algorithm of actions for an emergency medical team doctor or paramedic in NSTE-ACS

1. Taking complaints and medical history, assessing pain syndrome, physical examination, monitoring hemodynamic parameters (BP, HR) are recommended.

2. Restriction of physical activity is recommended.

3. ECG recording in at least 12 leads and remote ECG consultation (if necessary and feasible) are recommended.

4. Starting continuous ECG monitoring, establishing intravenous access, and ensuring readiness for defibrillation and cardiopulmonary resuscitation are recommended.

4. Emergency hospitalization to a hospital included in the ACS patient routing system is recommended.

If criteria for a high risk of adverse ischemic events are present (persistent or recurrent pain syndrome, ongoing ST-segment shifts on ECG, unstable hemodynamic parameters/shock, pulmonary edema, life-threatening ventricular arrhythmias/intracardiac conduction disorders or cardiac arrest, suspicion of mechanical complications of MI), emergency hospitalization of patients to a facility capable of performing PCI within 2 hours of admission is indicated. The receiving hospital must be informed about the transportation of an unstable patient.

5. Thrombolytic therapy is not recommended for patients with NSTE-ACS.

6. Relief of pain syndrome is recommended.

In the absence of arterial hypotension and other contraindications, nitroglycerin** is recommended at a dose of 0.4–0.5 mg as sublingual tablets or an 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, continuous blood pressure monitoring is required.

If the pain syndrome persists after 3 doses of nitroglycerin**, intravenous administration of a narcotic analgesic is necessary. The dose of the narcotic analgesic required for adequate pain relief must be selected individually. Morphine** is the drug of choice. 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 min in doses of 2–4 mg until pain relief is achieved or side effects occur that preclude dose escalation.

6. In the absence of contraindications, the use of acetylsalicylic acid at a dose of 150–300 mg is recommended (chewed; enteric-coated oral dosage forms of the drug are not recommended).

7. The use of a P2Y₁₂ platelet receptor inhibitor and anticoagulants is not recommended.

9. Treatment of acute heart failure and life-threatening heart rhythm and conduction disorders should be provided in accordance with section 3.4 of these Guidelines.

10. The ambulance dispatch sheet and accompanying slip should indicate the time of ACS onset, time of first medical contact, time of ECG recording, prehospital treatment provided with drug doses, and time of patient delivery to the hospital. If known, it is recommended to indicate medications taken by the patient in the preceding 24 hours, their administration times, and doses.

Appendix C. Patient Information

Acute coronary syndrome is a period of exacerbation of coronary artery disease when the probability of myocardial infarction and death is highest. The most frequent manifestation of myocardial ischemia is chest pain or discomfort. In cases where these sensations have recently appeared, become more frequent or severe—especially if they begin to occur at rest, with minor physical exertion, or take a prolonged course—it is urgent to seek medical help (optimally, call an ambulance). In such a situation, it is important to assess the severity of disease manifestations, the danger of complications, and timely detect other diseases that contribute to the occurrence of acute coronary syndrome, exacerbate its severity, or resemble it in their manifestations. Only a physician can do this. If the presence of acute coronary syndrome is confirmed, the physician will choose the optimal treatment method, which, along with medications in the form of tablets, injections, and infusions, may include X-ray examination of the heart vessels, which in many cases cannot be delayed. Based on the results of this study, it will become clear whether there is a need to restore coronary vessel patency, and if so, how and how urgently this needs to be done.

It is important to understand that in most cases, acute coronary syndrome is a manifestation of the progression of atherosclerosis, which develops in all human arteries. Therefore, after discharge, the elevated threat of a recurrence of complications associated with the disruption of atherosclerotic plaques leading to thrombosis will persist for a long time. Therefore, it is very important not to stop the treatment started in the hospital and to focus efforts on eliminating factors contributing to the progression of atherosclerosis (stop smoking, ensure regular physical activity, adhere to a diet designed for such cases, get rid of excess body weight, maintain low blood cholesterol levels, ensure stable normalization of blood pressure in case of arterial hypertension, and maintain normal blood sugar levels in case of diabetes mellitus). Premature discontinuation of certain medications significantly increases the risk of myocardial infarction and death from coronary artery disease, so this must not be done without consulting a physician.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Assessment of adverse outcome risk in NSTE-ACS using the GRACE scale

Original name: GRACE (The Global Registry of Acute Coronary Events) risk score

Source: Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al.; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003 Oct 27;163(19):2345-53. doi: 10.1001/archinte.163.19.2345.

Type (underline): rating scale, index, questionnaire, other (specify).

Purpose: a standardized method for determining the in-hospital mortality risk level in patients with NSTE-ACS based on a list of criteria present at the time of hospital admission.

Content:

Key (interpretation):

Notes:

* Cardiac troponin of "conventional" sensitivity was used when developing this scale.

Other variants of the GRACE 1.0 scale for assessing the long-term prognosis of the disease, as well as the combined endpoint of death and MI, are available on the Internet at: https://www.outcomes-umassmed.org/grace/acs_risk/acs_risk_content.html [109, 113-119].

An improved variant of the GRACE scale (GRACЕ 2.0) is available on the Internet at: https://www.outcomes-umassmed.org/grace/acs_risk2/index.html [119].

An improved variant of the GRACE scale (GRACЕ 3.0) is available on the Internet at: https://www.grace-3.com [122].

Appendix G2. High Bleeding Risk Scale of the Academic Research Consortium for patients undergoing planned/completed PCI and/or 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 [123].

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:

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 G3. Assessment of major bleeding risk in patients with NSTE-ACS during hospitalization (CRUSADE scale)

Original name: CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) bleeding score

Source:

1. Hoekstra JW, Pollack CV Jr, Roe MT, Peterson ED, Brindis R, Harrington RA, et al. Improving the care of patients with non-ST-elevation acute coronary syndromes in the emergency department: the CRUSADE initiative. Acad Emerg Med. 2002 Nov;9(11):1146-55. doi: 10.1111/j.1553-2712.2002.tb01569.x. PMID: 12414463.

2. Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation. 2009 Apr 14;119(14):1873-82. doi: 10.1161/CIRCULATIONAHA.108.828541.

Type (underline): rating scale, index, questionnaire, other (specify).

Purpose: a standardized method for assessing the risk of major bleeding in patients with NSTE-ACS during hospitalization.

Content:

Key (interpretation):

Notes: HR – heart rate, BP – blood pressure, DM – diabetes mellitus.

Appendix G4. Bleeding risk prediction to determine the duration of dual antiplatelet therapy in patients with indications for it (PRECISE-DAPT score)

Original name: Predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score

Source: Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Zanchin T, Palmerini T, Wallentin L, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: A pooled analysis of individual-patient datasets from clinical trials. Lancet 2017; 389: 1025-1034.

Type (underline): rating scale, index, questionnaire, other (specify).

Purpose: The PRECISE-DAPT score was developed to predict bleeding complications in patients with indications for dual antiplatelet therapy (aspirin plus a P2Y₁₂ platelet receptor inhibitor) to determine its duration.

Content:

Key (Interpretation): On the scale for each criterion, a point corresponding to the patient's level of this risk factor is located. A perpendicular line is drawn downwards from this point to the "points" scale. Its intersection with the "points" scale determines the weight of this criterion in points. The points are then summed up. The total score can range from 0 to 100.

Total score ≥ 25 — short-term dual antiplatelet therapy is recommended.

Total score < 25 — standard / prolonged dual antiplatelet therapy is recommended.

Notes:

CrCl – creatinine clearance;

Electronic version available at: http://www.precisedaptscore.com/predapt/webcalculator.html

Appendix G5. Determination of the risk of significant bleeding in patients with ACS using the ORACUL scale developed in a domestic patient population

Original name: ORACUL scale

Source: Brazhnik VA, Minushkina LO, Guliev RR, Averkova AO, Rogozhina AA, Koroleva OS, Zubova EA, Karmanchikova EA, Khasanov NR, Chichkova MA, Boeva OI, Galyavich AS, Zateyshchikov DA. Bleeding risk factors in patients with acute coronary syndrome: data from the ORACUL II observational study. Russian Journal of Cardiology. 2019; 24: 7-16.

Type (underline): rating scale, index, questionnaire, other (specify).

Purpose: The Oracul scale was developed in a domestic patient population to assess the risk of bleeding requiring any medical intervention in patients after ACS over the subsequent 12 months.

Content:

Key (interpretation):

Notes:

The scale was developed for patients with any type of ACS, including NSTE-ACS.

Here, significant bleeding refers to type 2–5 bleeding according to the BARC scale [52], i.e., any bleeding requiring additional medical interventions (diagnostic and/or therapeutic) [634].

Electronic version of the scale is available at: https://oracul.msk.ru/calculators/index.

PCI — percutaneous coronary intervention.