List of Abbreviations
VKA – vitamin K antagonists
ASA – acetylsalicylic acid**
ATC – Anatomical Therapeutic Chemical classification
CA – direct contrast angiography (direct lower extremity artery angiography)
AFB – aortofemoral bypass (NMU – A16.12.038.012 – aortoprofundoplasty / aorto-deep femoral bypass)
AFBB – aortofemoral bifurcation bypass (NMU – A16.12.038.010)
LEA – lower extremity arteries
FPB – femoropopliteal bypass (NMU – A16.12.038.006 – femoropopliteal bypass)
ICA – brachiocephalic arteries
PCD – pain-free walking distance
UD – lower extremity arterial ultrasound Doppler (NMU – A04.12.001.001)
PAD – peripheral artery disease
ИМ – myocardial infarction
CLTI – chronic limb-threatening ischemia
CTAG – computed tomography angiography of lower extremity vessels (NMU – A06.12.053)
ABI – ankle-brachial index
MA – mechanical atherothrombectomy (NMU – A16.12.003.001 – endovascular aspiration thrombectomy)
INR – international normalized ratio
MWD – maximal walking distance
MRA – magnetic resonance angiography (local medical service code: A05.12.007 – magnetic resonance angiography (one region))
LLLT – low-level laser therapy
CFA – common femoral artery
SFA – superficial femoral artery
PopA – popliteal artery
PTFE – polytetrafluoroethylene
IC – intermittent claudication
SE – semi-closed endarterectomy (local medical service code: A16.12.008 – endarterectomy)
DES – drug-eluting peripheral stents
LCE – level of confidence of evidence
GRS – grade of recommendation strength
EECP – enhanced external counterpulsation (local medical service code: A21.30.007 – external counterpulsation)
CKD – chronic kidney disease
CLTI – chronic lower limb ischemia
CLTI – chronic limb-threatening ischemia
PA – physical activity
Terms and Definitions
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, and treatment of diseases, rehabilitation, as well as for the maintenance, prevention, or termination of pregnancy.
Patient – an individual who receives medical care or who applies for medical care regardless of the presence of a disease and their condition.
Primary antithrombotic prophylaxis – prevention of atherothrombotic complications presenting as acute ischemia or chronic critical limb ischemia in patients with chronic obliterating diseases of the lower limb arteries without clinical symptoms of arterial ischemia or at the intermittent claudication stage.
Intermittent claudication – a long-standing clinical condition characterized by impaired patency of the major lower limb arteries and the occurrence of muscle pain or discomfort during walking, which resolves or decreases with brief rest.
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.
Symptom – a sign of a disease, a statistically significant deviation of a certain parameter from the limits of its normal values, or the emergence of a qualitatively new phenomenon uncharacteristic of a healthy body.
Syndrome – a stable set of several symptoms with a single pathogenesis.
Condition — changes in the body resulting from the impact of pathogenic and/or physiological factors that require medical care.
Drug-eluting peripheral stent – a stent for peripheral arteries from whose structures an antiproliferative agent is released for a certain period after placement, preventing neointimal hyperplasia and thereby helping to prevent or slow down restenosis.
Thesis-recommendation – a statement reflecting the procedure and correctness of performing a particular medical intervention with proven efficacy and safety.
Level of evidence reliability – the degree of confidence that the observed effect of a medical intervention is true.
Level of Evidence (LoE) – the degree of certainty in the reliability of the intervention's effect and that following the recommendations will bring more benefit than harm in a specific situation.
Surgical (open) revascularization – a method for correcting hemodynamically significant changes in an arterial segment of a limb, which necessarily involves the division and connection of tissues during a surgical operation.
Chronic lower limb ischemia – a long-standing clinical condition characterized by impaired arterial patency, progressing from symptoms of discomfort and pain during physical exertion in the buttock, thigh, or calf to trophic tissue defects of the limb.
Endovascular (endovasal) intervention – restoration of blood flow in the stenotic segment of the limb arterial bed using percutaneous introduction of the necessary devices. Includes transluminal balloon angioplasty, stenting, and other less common techniques.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Chronic lower limb ischemia (CLLI) – a long-standing clinical condition characterized by impaired arterial patency, progressing from symptoms of discomfort and pain during physical exertion in the buttock, thigh, or calf to trophic tissue defects of the limb.
One of the earliest and diagnostically significant symptoms of CLLI is intermittent claudication.
Intermittent claudication (IC) is a long-standing clinical condition characterized by impaired patency of the major lower limb arteries and the occurrence of muscle pain or discomfort during walking, which resolves or decreases with brief rest.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The spectrum of potential causes for IC includes diseases and pathological conditions leading to impaired patency of the lower limb arteries: atherosclerosis, thromboembolism, thrombosis, arteritis, as well as restenosis and thrombotic complications of reconstructions performed on limb arteries for arterial insufficiency.
According to the Framingham Heart Study, which analyzed risk factors for peripheral artery disease (PAD), advanced age, smoking, diabetes, hypertension, and hypercholesterolemia were established as the main risk factors associated with the development of peripheral artery atherosclerosis. Elevated inflammatory markers, including high-sensitivity C-reactive protein, interleukin-6, fibrinogen, ICAM-1, asymmetric dimethylarginine, beta-2 microglobulin, and cystatin C, are novel risk factors whose clinical significance in predicting the development of peripheral artery atherosclerosis has not yet been established [1].
Sex. The prevalence of lower extremity artery disease (LEAD), symptomatic or asymptomatic, is slightly higher in men than in women, especially in younger age groups. In patients with intermittent claudication (IC), the male-to-female ratio ranges from 1:1 to 2:1. In advanced stages of the disease, such as chronic critical limb ischemia, this ratio reaches 3:1 or more in some studies. Other studies have observed a more even distribution of LEAD between sexes and even a female predominance among patients with LEAD.
Age. Both the incidence and prevalence of LEAD increase sharply with age. According to the Framingham Heart Study, which analyzed risk factors for peripheral artery disease (PAD), advanced age was established as one of the main risk factors associated with the development of peripheral artery atherosclerosis.
Smoking is one of the main risk factors for LEAD. It contributes to the development of LEAD 2–3 times more frequently than coronary artery disease. Large epidemiological studies have revealed that smoking increases the risk of developing LEAD by 2–6 times, and IC by 3–10 times.
Diabetes mellitus (DM) increases the risk of LEAD by 2–4 times and is present in 10–40% of patients with peripheral arterial pathology, reaching 50% in the presence of chronic lower limb trophic ulcers. Progression of LEAD can lead to critical limb ischemia [2, 3]. According to the Framingham Heart Study, DM increases the risk of IC by 3.5 times in men and 8.6 times in women. DM has been established to be a factor worsening long-term outcomes of arterial reconstructions in limb ischemia [4].
Lipid metabolism disorders in LEAD manifest as elevated total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, decreased high-density lipoprotein (HDL) cholesterol, and hypertriglyceridemia. With a 10 mg/dL increase in total cholesterol, the risk of developing LEAD increases by approximately 5–10%. Epidemiological studies noted a more significant elevation in total cholesterol levels in patients with IC than in individuals without LEAD. LDL levels were higher in patients with LEAD and lower in those without peripheral arterial pathology in age-matched groups. The relationship between hypertriglyceridemia and LEAD remains incompletely understood.
Arterial hypertension correlates with LEAD, although the association is weaker than with cerebrovascular and coronary pathology. In some studies, arterial hypertension (AH) increases the risk of LEAD, while in others it does not. According to the Framingham Heart Study, AH increases the risk of developing IC by 2.5 and 4 times in men and women, respectively, with the risk being proportional to the severity of arterial hypertension.
1.3 Epidemiology of the Disease or Condition
The main cause of intermittent claudication is atherosclerosis obliterans. According to a large population-based prospective study, the National Health and Nutrition Examination Survey (NHANES), the proportion of people with an ankle-brachial index (ABI) below 0.9 was 4.64% in the general population, increasing from 1.43% in the 40–49 age group to 16.62% in the ≥72 age group. The main risk factors, aside from age, were smoking (RR 4.1; 95% CI: 3.1–5.4), chronic kidney disease (RR 2.0; 95% CI: 1.4–2.7), diabetes mellitus (RR 1.5; 95% CI: 1.0–2.3), hypertension (RR 1.5; 95% CI: 0.9–2.2), and hypercholesterolemia (RR 1.3; 95% CI: 1.0–1.8). The presence of two risk factors increased the probability of detecting an ABI <0.9 by 3.6-fold, and the presence of three or more risk factors by 8.9-fold [5].
As with any occlusive disease of the arterial bed, the mere presence of arterial patency disorders does not necessarily lead to clinical symptoms of arterial insufficiency. According to a prospective study of chronic diseases in the elderly (the Rotterdam Study), the prevalence of intermittent claudication (IC) symptoms among patients with proven reduction in ABI was only 6.3%. Conversely, among patients with IC symptoms, only 68.9% were found to have an ABI <0.90 [6].
In addition to the primary cause—atherosclerosis obliterans—IC may be caused by limb artery thrombosis, aortoarteritis, cystic adventitial degeneration, popliteal artery entrapment syndrome, and several other rare diseases [7, 8, 9, 11].
1.4 Features of Coding the Disease or Condition
The IC syndrome is based on a wide spectrum of diseases and medical conditions listed in clause 3 of Section V of these clinical guidelines. Possible coding options for these nosological forms according to the International Classification of Diseases (10th revision) are listed below:
I70.2 – Atherosclerosis of extremities' arteries
I72.4 – Aneurysm of lower extremity artery
I77.1 – Stricture of artery
I77.3 – Arterial fibromuscular dysplasia
I77.6 – Arteritis, unspecified
E10.5 – Insulin-dependent diabetes mellitus with peripheral circulatory complications
I73.1 – Thromboangiitis obliterans [Buerger's disease]
I73.9 – Peripheral vascular disease, unspecified (IC)
1.5 Classification of the disease or condition
The concept of IC corresponds to stage 2 of chronic lower limb arterial insufficiency according to the Pokrovsky-Fontaine classification (stage 1 according to the Rutherford classification) and includes patients with a sensation of discomfort or pain in any group of lower extremity muscles that invariably occurs during physical exertion and subsides at rest. Most often, these unpleasant sensations are localized in the calf muscles, but they can also occur in other segments of the limb (Table 1). Symptoms usually remain stable for many years, and only in isolated cases does the disease progress to CLTI [12]. According to large prospective studies, the 10-year incidence of minor and major amputations in patients with IC is less than 10% [13, 14]. At the same time, a significant proportion of patients may develop symptoms of critical limb ischemia (up to 30%), and 18% of them require limb revascularization [14].
According to the severity of intermittent claudication symptoms, the following are distinguished:
Mild IC (clinically insignificant, not affecting the quality of life), which corresponds to stage 2A according to the Fontaine-Pokrovsky classification and stage 1 (category 1) according to the Rutherford classification.
Clinically significant (moderate or severe) IC, which corresponds to stage 2B according to the Fontaine-Pokrovsky classification and stage 1 (categories 2-3) according to the Rutherford classification.
It should be borne in mind that in patients with diabetes mellitus, the use of the Fontaine-Pokrovsky and Rutherford classifications is impractical, as it does not reflect the severity of chronic arterial insufficiency in diabetic angiopathy, where trophic disorders can develop at any stage of the disease [10].
1.6 Clinical presentation of the disease or condition
Typical clinical manifestations of intermittent claudication are discomfort and/or pain in various segments of the lower extremity that occur during physical exertion and resolve rather quickly at rest. It should be noted that there are several musculoskeletal and nervous system disorders capable of producing very similar clinical manifestations. Table 1 (adapted from the Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease) presents the diseases and syndromes that form the differential diagnosis of IC [15].
Table 1. Differential diagnosis of intermittent claudication (IC) (based on the materials of the Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease)
Condition | Pain localization | Clinical manifestations | Effect of exercise | Effect of rest | Effect of body position | Other characteristics |
|---|---|---|---|---|---|---|
Calf IC | Calf muscles | Cramps, aching pain, discomfort | Repetitive attack | Rapid relief | No | Atypical lower extremity symptoms may occur during exercise |
Thigh IC | Buttock, thigh, | Cramps, aching pain, discomfort | Repetitive attack | Rapid relief | No | Impotence. Standard leg pulses may be present with isolated iliac artery disease |
Foot IC | Sole of the foot | Severe pain with exercise | Repetitive attack | Rapid relief | No | Numbness may also be felt |
Chronic compartment syndrome | Calf muscles | Pronounced bursting pain | Following significant physical exertion (e.g., running) | Subsides very slowly | Relief occurs with limb elevation | Usually observed in athletes with high muscle mass |
Venous claudication | Entire limb, more severe calf pain | Non-relieving bursting pain | After walking | Subsides slowly | Relief occurs faster with elevation | History of iliofemoral deep vein thrombosis, signs of venous stasis, edema |
Compressive radiculopathy | Pain radiating down the limb, usually along the posterior aspect | Sharp shooting pain | Triggered by sitting, standing, walking | Usually occurs at rest | Improvement occurs with a change in position | History of back problems. Worsens in the sitting position. Improves in the supine or standing position. |
Baker's cyst | Popliteal fossa and posterior calf | Local swelling, puffiness, tenderness | Occurs against the background of physical exertion | Persists at rest | Does not affect | Symptoms are not intermittent in nature |
Coxarthrosis | Lateral aspect of the thigh | Aching pain, discomfort | Occurs after physical activity of varying intensity | Gradually subsides | Improvement in the absence of axial loads on the limb | Variability of symptoms, history of coxarthrosis |
Spinal stenosis | Pain is often bilateral, localized in the buttocks and along the posterior aspect of the thigh and leg | Pain and muscle weakness | May resemble IC | The time required for pain regression is variable and may be quite long | Decreases with lumbar spine flexion | Increases in the standing position and with lumbar spine extension |
Ankle or foot joint arthritis | Ankle region, foot bones, arch of the foot | Aching pain | Occurs after physical activity of varying intensity | Slow regression of pain | Possible improvement in the absence of axial loads on the limb | Variable nature of clinical manifestations, which may also be present at rest. Symptom intensity may depend on the level of physical activity. |
2. Diagnostics, medical indications and contraindications for diagnostic methods
Criteria for establishing a diagnosis based on pathognomonic findings:
History of intermittent claudication episodes—painful sensations in the lower extremity during physical exertion that resolve after a short rest. The pain can be unilateral or bilateral; localization depends on the level of arterial lesion.
Physical examination: weakened arterial pulsation at various levels, loss of hair in the distal extremities, muscle atrophy, delayed capillary refill time.
Instrumental examination: presence of steno-occlusive lesions of the main arteries of the limb.
2.1 Complaints and Anamnesis
It is recommended to conduct a detailed patient interview to clarify complaints, medical history, and risk factors in all patients with IC [15, 16].
(LoE 5, GoR C)
Comments: when elucidating complaints, it is necessary to pay attention to the characteristic symptoms of IC and perform differential diagnosis of this pathology with other clinical syndromes (see Section 3.6). When taking the medical history, attention should be paid to the presence of risk factors and comorbid conditions typical for IC (see Section 3.3), previous arterial reconstructions, concurrent drug therapy, especially antiplatelet agents and anticoagulants (ATC code B01A Antithrombotic agents). In other aspects, the patient interview for IC is conducted according to the general principles of clinical medicine.
2.2 Physical Examination
It is recommended that the patient undergo an initial consultation (examination, consultation) with a cardiovascular surgeon to collect complaints and medical history, perform a general physical examination of a patient with IC in accordance with the principles of clinical medicine to assess the systemic involvement of the vascular bed [15, 16].
(LoE 5, GoR C)
Comments: the collection of complaints, examination, and evaluation of a patient with vascular pathology are carried out in accordance with the general principles of clinical medicine. When examining the cardiovascular system, it is useful to pay attention to signs of impaired patency of the upper extremity arteries (decreased pulsation of the brachial and radial arteries, presence of a systolic murmur in the projection of the subclavian arteries, blood pressure differences between the upper extremities) due to their potential use for endovascular access.
It is recommended to assess the local status of the limb, including inspection and palpation, to identify objective signs of impaired arterial blood flow in the limb [17, 18, 19, 20, 21, 22].
(LoE 2, GoR B)
Comments: assessment of arterial pulsation at various levels has the highest sensitivity and specificity in this regard; auscultation of the femoral arteries has lesser diagnostic value. Important, although less significant, additional signs may include the loss of hair in the distal parts of the extremities, muscle atrophy, delayed capillary refill time (more than 2 seconds, according to other data more than 5 seconds), and pallor of the plantar surface of the foot after elevating the limb (plantar ischemia sign).
2.3 Laboratory Diagnostics
Quality studies and detailed recommendations on laboratory diagnostics in IC are lacking in the literature. Therefore, the choice of laboratory parameters throughout the treatment period should be based on the general principles of clinical medicine and determined individually for each patient by the members of the vascular team.
It is recommended to perform a complete blood count (CBC), general biochemical blood test (levels of creatinine, blood urea, ALT, AST activity, sodium, potassium, total bilirubin, blood glucose, and serum C-reactive protein) upon initial presentation and during follow-up to assess cardiovascular risk and the patient's condition [23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37].
(LoE 4, GoR C)
Comments: a complete blood count and general biochemical blood tests are routinely performed upon initial presentation and twice a year during follow-up control visits.
2.4 Instrumental Diagnostics
The main objectives of instrumental diagnostics in IC are to confirm the steno-occlusive lesion of the main arteries of the limb, determine its nature and localization for planning potential reconstructive intervention, and provide intraoperative and postoperative control of revascularization. A secondary objective is to identify clinically significant comorbid conditions of internal organs that affect the level of perioperative risk.
The most common and studied vascular imaging methods in IC are lower extremity arterial duplex ultrasound (DUS) (NMES – A04.12.001.001), computed tomography angiography of lower extremity vessels (CTA) (NMES – A06.12.053), direct contrast angiography (DSA) (NMES – A06.12.039 Direct angiography of lower extremity arteries), and magnetic resonance angiography (MRA) (NMES – A05.12.007). All of them have sufficiently high sensitivity and specificity (Table 2) [38, 39, 40, 41, 42, 43].
Table 2. Comparative analysis of various vascular imaging methods in IC compared to digital subtraction angiography as the diagnostic "gold standard" [44]
Sensory function | Specificity | Advantages | Disadvantages | |
|---|---|---|---|---|
Lower extremity arterial duplex ultrasound | > 85% | > 95 % | Low cost, no radiation exposure, non-invasive | Operator-dependent technique, accuracy depends on individual patient characteristics, labor-intensive, low accuracy of examination below the knee |
Computed tomography angiography of lower extremity vessels | > 90 % | > 90 % | Visualization of the entire vascular bed, relatively short procedure, non-invasive | Radiation exposure, inaccurate interpretation of results in cases of severe vascular calcification, nephrotoxicity of the contrast agent |
Magnetic resonance angiography | > 90 % | > 90 % | Visualization of the entire vascular bed, non-invasive, no radiation exposure | Relatively high cost, contraindications (presence of ferromagnetic implants, claustrophobia), risk of gadolinium-induced nephrogenic systemic fibrosis |
Direct angiography of lower extremity arteries | _ | _ | Visualization of the entire vascular bed, possibility of immediate intervention | Relatively high cost, invasiveness, radiation exposure, nephrotoxicity of the contrast agent |
It is recommended to perform lower extremity arterial duplex ultrasound (NMES-A04.12.001.001) with determination of the ankle-brachial index (ABI) for initial vascular imaging in patients with clinical signs of IC [45, 41].
(LoE 1, GoR B)
Comments: duplex ultrasound is the most non-invasive and accessible of the listed methods, which is why vascular imaging should begin with it in the presence of IC symptoms. According to a meta-analysis of retrospective studies, an ABI value ≤0.90 has a sensitivity of 75% and a specificity of 86% as a diagnostic test for detecting hemodynamically significant changes in limb arteries [46].
In incompressible crural arteries (ABI ≥1.4), plethysmographic assessment of the toe-brachial index (TBI) is used. According to a meta-analysis of retrospective studies, this test has a sensitivity of 81% and a specificity of 77% in diagnosing hemodynamically significant limb artery lesions [47]. Also, in moderate limb artery disease, when resting ABI values are borderline and the diagnosis of intermittent claudication is in doubt, this value can be assessed after physical exertion (walking). In a retrospective study by Tehan et al., a decrease in ABI ≤0.90 after graded walking (for 5 minutes) had a sensitivity of 70.76% and a specificity of 71.43% in diagnosing occlusive limb artery disease [48].
It is recommended to perform non-invasive imaging (duplex ultrasound, CTA, MRA), or invasive imaging (angiography) if non-invasive methods are unavailable, when planning limb revascularization in patients with a confirmed diagnosis of intermittent claudication [44].
(Letvel of Evidence 5, Grade of Recommendation C)
It is recommended to visualize the saphenous veins intended for use as an autologous conduit prior to femoropopliteal bypass surgery to aid in limb revascularization planning [49].
(Level of Evidence 5, Grade of Recommendation C)
Comments: arterial imaging is used to plan limb revascularization [49]. Some experienced vascular teams successfully use duplex ultrasound for this purpose without resorting to other modalities (CTA, angiography, and MRA) [41, 50, 51, 52, 53]. In chronic kidney disease (CKD), using duplex ultrasound at this stage of treatment helps reduce the cumulative dose of nephrotoxic contrast media or avoid its use altogether. Certain prospects in this area are also associated with the introduction of carbon dioxide angiography into clinical practice [54], which is, however, an invasive technique.
Immediately prior to limb artery bypass surgery, some authors recommend performing Doppler ultrasound of the arteries to assess the quality and diameter of the saphenous veins before surgery, as well as to map the course of the vein on the skin surface [16, 55]. Furthermore, according to Belvedere et al., Doppler ultrasound is a more accurate method for assessing the condition of a potential venous conduit than CTA [56].
It is recommended that patients with intermittent claudication undergo a comprehensive evaluation of other arterial beds (coronary, cerebral), functional assessment of the cardiovascular system, and examination of other organs and systems in accordance with general clinical practice principles, guidelines of specialized societies, and expert opinion from relevant multidisciplinary vascular team specialists [57].
(Level of Evidence 5, Grade of Recommendation C)
Comments: patients with chronic peripheral artery disease (even asymptomatic) are at high cardiovascular risk. Atherosclerosis is typically characterized by multi-vessel disease affecting several arterial beds simultaneously [58]. Patients older than 65 years, those with diabetes mellitus, and those with chronic kidney disease require special attention. Early diagnosis and prevention of cardiovascular diseases are critically important for them. However, patients with intermittent claudication do not routinely require coronary imaging prior to lower limb revascularization, nor do they need routine screening for stenoclusive brachiocephalic artery disease or erosive and ulcerative lesions of the stomach and duodenal mucosa.
2.5 Other Procedures
Not required.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
Conservative management of patients with lower extremity arterial disease should aim to reduce the risk of cardiovascular events by modifying or completely eliminating risk factors for atherosclerotic disease (cigarette smoking, diabetes mellitus, dyslipidemia, and arterial hypertension), maintaining daily physical activity, and relieving symptoms directly related to lower extremity vascular lesions. These principles should apply to the treatment of patients at all stages of the disease, including the asymptomatic stage.
3.1.1 Reduction of the risk of cardiovascular complications
3.1.1.1 Smoking cessation
It is strongly recommended that patients with lower extremity arterial disease who smoke or use tobacco in any other form quit smoking to reduce the risk of cardiovascular events and disease progression. A comprehensive approach is recommended for this purpose, including behavioral modification techniques and pharmacotherapy for nicotine dependence [59, 60, 61, 62].
(Level of Evidence 2, Grade of Recommendation B)
Comments: tobacco smoking is a major risk factor for the development and progression of lower extremity arterial disease, increasing the need for revascularization procedures and the risks of critical limb ischemia and amputations [63]. Motivation to quit smoking should be an important part of patient counseling. Even a verbal recommendation from a physician can serve as a trigger for smoking cessation [64]. However, the most effective method for smoking cessation is a combination of lifestyle changes and pharmacotherapy [65, 66, 67]. Electronic cigarettes can be used as an auxiliary smoking cessation tool since, according to a Cochrane review, they increase the number of successful quitters compared to nicotine replacement therapy [68]. However, it should be borne in mind that e-cigarettes have adverse effects on the cardiovascular, respiratory, and immune systems as well as dental health; therefore, their use should be short-term only during the smoking cessation phase [69, 70].
Smoking cessation as a measure to reduce the risk of late arterial graft occlusion.
It is strongly recommended that all patients with intermittent claudication who have undergone lower limb revascularization quit smoking to reduce the risk of patency loss in endovascular arterial reconstructions [71].
(Level of Evidence 2, Grade of Recommendation B)
Comments: according to a meta-analysis of 29 studies (including 4 randomized controlled trials), smoking cessation following lower extremity arterial bypass surgery resulted in a 3.09-fold reduction in the long-term risk of graft occlusion (95% CI: 2.34–4.08; p < 0.00001). Among the randomized trials, conduit patency data were reported in only one. The proportion of patients with chronic limb-threatening ischemia in the study was not specified, and subgroup analysis for intermittent claudication was not performed [71].
3.1.1.2 Lipid-lowering therapy
It is recommended to treat all patients with clinical manifestations of lower extremity arterial disease with HMG-CoA reductase inhibitors to reduce the risk of cardiovascular events and the progression of lower extremity arterial disease [88, 73, 74, 75, 76].
(Level of Evidence 1, Grade of Recommendation B)
Comments: all patients with dyslipidemia are indicated for statin therapy (HMG-CoA reductase inhibitors) at doses required to achieve the target LDL-C level [73, 74, 75, 76].
Management of dyslipidemia reduces the risk of adverse cardiovascular events in patients with atherosclerosis. Lipid-lowering therapy with HMG-CoA reductase inhibitors (statins) reduces the risk of non-fatal myocardial infarction and cardiovascular death in patients with coronary artery disease by 24–34%. The Heart Protection Study included 6,748 patients with chronic lower extremity ischemia (with coronary artery disease, stroke, peripheral arterial disease, and/or diabetes mellitus, and total cholesterol > 135 mg/dL) randomized to simvastatin** or placebo, which demonstrated a 25% risk reduction over a five-year follow-up period [73]. In accordance with the consensus statement of the European Society for Vascular Surgery, statin therapy is also indicated for asymptomatic patients with peripheral arterial disease to reduce the risk of cardiovascular events, limb complications, and lower extremity arterial disease progression [44].
It is recommended to prescribe HMG-CoA reductase inhibitors (statins) to all patients with type 1 diabetes mellitus older than 40 years who have not reached the target LDL-C level, regardless of the presence of coronary artery disease or other cardiovascular pathology, to prevent the progression of atherosclerotic cardiovascular disease and complications [77, 78, 79].
(LoE 5, GoR C)
It is recommended to prescribe HMG-CoA reductase inhibitors (statins) to all patients with clinical manifestations of lower extremity arterial disease and type 2 diabetes mellitus at high and very high cardiovascular risk, as well as patients with type 2 diabetes at moderate risk who have not reached the target LDL-C level, regardless of the presence of coronary artery disease and other cardiovascular pathology, to reduce the risk of cardiovascular events [80, 82, 83, 84].
(Level of Evidence 1, Grade of Recommendation A)
It is recommended to treat with HMG-CoA reductase inhibitors (statins) to achieve a target LDL cholesterol level of < 1.4 mmol/L (55 mg/dL) and at least a 50% reduction in LDL cholesterol from baseline [73, 87, 90, 91, 92, 93, 94].
(LoE 5, GoR C)
Comments: in patients with peripheral artery disease, statin therapy not only significantly reduces mortality and the number of cardiovascular events [79, 80], but also decreases the number of adverse limb events and increases walking distance [94, 95, 97]. If high-intensity statin therapy at maximally tolerated doses fails to achieve LDL-C target levels in patients at high risk of cardiovascular complications, ezetimibe 10 mg/day should be added to the therapy to inhibit cholesterol absorption in the small intestine, preferably in a single tablet or capsule (rosuvastatin+ezetimibe and atorvastatin+ezetimibe are registered) [94, 98, 99, 101]. In very high-risk patients who do not reach the target LDL-C level on maximally tolerated statin doses combined with ezetimibe, alirocumab** (ESC/EAS I A), evolocumab** (ESC/EAS I A), or inclisiran** (ESC/EAS no data) should be added for secondary prevention of CVD [100, 101, 102, 103].
It is recommended to prescribe a selective intestinal cholesterol absorption inhibitor, ezetimibe (ATC classification C10AX other lipid-modifying agents), to patients with type 1 diabetes mellitus and coronary artery disease at very high cardiovascular risk with atherosclerotic lesions in multiple vascular beds or recurrent atherothrombotic events and insufficient LDL-C reduction on maximally tolerated doses of HMG-CoA reductase inhibitors (statins), in order to achieve the target LDL-C level and reduce the risk of cardiovascular events [104].
(LoE 5, GoR C)
It is recommended to prescribe a selective intestinal cholesterol absorption inhibitor (other lipid-modifying agents), ezetimibe, to all patients with clinical manifestations of lower limb artery disease and type 2 diabetes mellitus at high and very high cardiovascular risk with insufficient LDL-C reduction on maximally tolerated doses of HMG-CoA reductase inhibitors, in order to achieve the target LDL-C level and reduce the risk of cardiovascular events [105].
(LEL 2, GOR A)
3.1.1.3 Antihypertensive therapy
It is recommended for all patients with peripheral artery disease and hypertension receiving treatment, regardless of age and risk level, to lower blood pressure as a first target to <140/90 mm Hg, and, if well tolerated, to a target level of 130/80 mm Hg or lower, to reduce the risk of CVD events [107, 108, 1].
(LEL 1, GOR A)
It is recommended as starting therapy for all patients with peripheral artery disease and hypertension (except low-risk patients with BP <150/90 mm Hg, patients aged ≥80 years, and patients with frailty syndrome) to use a combination of antihypertensive drugs, preferably fixed-dose, to improve treatment adherence. Preferred combinations for most patients should include a renin-angiotensin system inhibitor (RASi) (ATC C09AA – angiotensin-converting enzyme (ACE) inhibitors) and calcium channel blockers (C08 – calcium channel blockers) or a diuretic [109, 110, 111, 112, 113].
(LEL 1, GOR A)
Comments: ACE inhibitors reduce the risk of death and non-fatal cardiovascular events in patients with coronary atherosclerosis. A study involving 11,331 patients (12,433 limbs) with chronic limb-threatening ischemia (CLTI) demonstrated that the use of ACE inhibitors and angiotensin II receptor blockers is independently associated with increased overall survival and amputation-free survival after revascularization interventions [123].
It is recommended to consider prescribing beta-blockers (ATC C07AB selective beta-blockers) as antihypertensive drug therapy for patients with peripheral atherosclerosis, especially when there are indications for their use to reduce symptom severity [129, 130, 131].
(LEL 2, GOR A)
Comments: the results of a meta-analysis of 11 placebo-controlled trials involving patients with intermittent claudication showed that beta-blockers did not worsen the clinical symptoms of the disease [129, 130, 131].
3.1.1.4 Antiplatelet agents and anticoagulants (antithrombotic agents)
Although patients with chronic lower limb ischemia are at very high cardiovascular risk, studies have not confirmed the efficacy of antiplatelet agents (ATC B01A antithrombotic agents) in reducing the risk of major adverse cardiovascular events and revascularizations in asymptomatic patients [103]. Therefore, antiplatelet therapy is not indicated for asymptomatic patients. An exception is made for patients with diabetes mellitus who, in the absence of contraindications, may be prescribed regular acetylsalicylic acid** 75-100 mg for primary and secondary prevention [129, 130]. Patients with hypertension combined with atherosclerotic cardiovascular diseases (coronary artery disease, prior myocardial infarction, cerebrovascular disease, atherosclerotic peripheral arterial disease) may be prescribed low-dose acetylsalicylic acid** for secondary prevention of CV events [132, 133, 134, 135, 136, 137, 138].
It is recommended to administer antiplatelet therapy to patients with lower limb artery disease and intermittent claudication to reduce the risk of myocardial infarction, stroke, or death [139, 140].
(Level of Evidence 1, Grade of Recommendation B)
Comments: in patients with symptomatic lower extremity artery disease, antiplatelet therapy improves cardiovascular prognosis [140, 141, 142, 143].
It is recommended to administer #acetylsalicylic acid** (ATC B01AC antiplatelet agents, excluding heparin) at a dosage of 75-150 mg as a safe and effective antiplatelet therapy for patients with lower limb artery disease to reduce the risk of myocardial infarction, stroke, or death [144].
(LoE 5, GoR C)
Comments: the efficacy of various dosages of #acetylsalicylic acid** was compared. The proportional reduction in the risk of vascular events was 32% with 75-150 mg daily, 26% with 160-325 mg daily, and 19% with 500-1500 mg daily, with results being relatively comparable; only a 13% risk reduction was observed with doses of less than 75 mg of #acetylsalicylic acid** daily. High doses of #acetylsalicylic acid** lead to gastrointestinal side effects and increase bleeding risk.
It is recommended to use clopidogrel** monotherapy (ATC B01AC antiplatelet agents excluding heparin) 75 mg daily in patients with intermittent claudication to reduce the risk of serious adverse limb events [142, 145].
(LEL 1, GOR A)
Comments: data from a systematic meta-analysis [107] demonstrate that clopidogrel** significantly more effectively reduced the risk of cardiovascular events compared to #ASA without increasing the bleeding risk, allowing clopidogrel** to be considered an effective alternative to #acetylsalicylic acid in the treatment of patients with lower limb artery disease [142, 145].
It is recommended to consider using a combination of #acetylsalicylic acid** (ATC B01AC antiplatelet agents, excluding heparin) at a dose of 100 mg daily with rivaroxaban** (ATC B01AF – direct factor Xa inhibitors) 2.5 mg twice daily for the primary prevention of cardiovascular complications and major amputations in patients with a confirmed diagnosis of lower extremity obliterating atherosclerosis in the stage of intermittent claudication and low bleeding risk [147, 148, 149].
(LEL 2, GOR A)
Comments: compared to #ASA monotherapy, dual antithrombotic therapy statistically significantly reduced the risk of the combined endpoint of cardiovascular death/myocardial infarction/stroke by 28%; the risk of major adverse limb events by 46%, the risk of major limb amputation by 70%, and the risk of unplanned vascular interventions for limb ischemia by 43%. At the same time, the risk of major bleeding events according to the modified International Society on Thrombosis and Haemostasis (ISTH) criteria in the dual therapy group was significantly higher than with #ASA monotherapy (3.1% vs. 1.9%; p=0.0089). The groups did not differ significantly in the frequency of fatal, intracranial, or critical organ bleeding [147].
It is not recommended to use oral anticoagulant therapy with warfarin** (ATC B01AA vitamin K antagonists) to reduce the risk of adverse cardiovascular ischemic events in patients with lower limb artery disease and intermittent claudication [150].
(LEL 1, GOR A)
3.1.2 Relief of symptoms of lower extremity vascular disease
3.1.2.1 Supervised exercise therapy (walking)
It is recommended to use therapeutic walking (medical service code A19.23.002.013 – terrain cure [walking therapy]) as a first-line treatment for intermittent claudication (supervised or self-directed) to relieve symptoms of lower extremity vascular lesions [151, 152, 153, 154, 155, 156, 157].
(LEL 2, GOR A)
Comments: aerobic exercise restores endothelial, mitochondrial, and myocyte function, promotes microvascular network remodeling, and reduces local inflammation. As a result of training, not only does pain in intermittent claudication decrease, but the functional state of the cardiovascular and respiratory systems, as well as the quality of life, also improves. Supervised or therapeutic walking should generally be continued until moderate or severe limb pain occurs [154, 155]. Positive dynamics can also be achieved with pain-free exercise and low-pain loads [156, 157].
According to a review of 23 studies involving 1,907 patients, supervised exercise training provides a more pronounced increase in maximum walking distance compared to unsupervised home-based exercise [147]. If supervised sessions are not feasible, self-directed exercises may be recommended, which should be planned with a gradual increase in exercise intensity (every 1-2 weeks) from low to maximum tolerated levels [153].
3.1.2.2 Pharmacotherapy
To increase pain-free walking distance in patients with intermittent claudication, antiplatelet agents (ATC Antiplatelet agents excluding heparin), anticoagulants (ATC Heparin group), angioprotectors (ATC Angioprotectors), tissue repair stimulants (ATC - Other therapeutic products), and vasodilators (ATC - Other peripheral vasodilators) are used. These drugs act directly or indirectly on the vascular wall. In clinical trials, the efficacy of any drug for the treatment of intermittent claudication is evaluated primarily by the dynamics of changes in pain-free walking distance (PFWD) or maximum walking distance (MWD), as well as by microcirculation study data and parameters reflecting the functional state of blood cells. The selection of drug therapy for each patient is determined by the specific clinical situation.
3.1.2.2.1 Cilostazol
It is recommended to use cilostazol (ATC B01AC – platelet aggregation inhibitors excluding heparin) to reduce symptoms and increase pain-free walking distance in patients with intermittent claudication [162, 163].
(LEL 1, GOR A)
Comments: cilostazol is the most studied medicinal product intended to reduce the symptoms of intermittent claudication and increase walking distance [162].
Cilostazol is prescribed at a dose of 100 mg orally twice a day. The positive effect of cilostazol on walking distance is achieved with regular drug intake. According to Dawson et al., discontinuation of therapy gradually leads to a return of clinical manifestations [164].
3.1.2.2.2 Naftidrofuryl
It is recommended to use naftidrofuryl (ATC C04AX – other peripheral vasodilators) to increase pain-free walking distance in patients with intermittent claudication [164].
(LEL 1, GOR A)
Comments: naftidrofuryl is a peripheral vasodilator, a 5-HT2 receptor antagonist that enhances aerobic metabolism and oxygen consumption in ischemic tissues. This drug is used in Europe to increase pain-free walking distance in patients with intermittent claudication [44]. A meta-analysis of 7 randomized double-blind placebo-controlled trials showed that the drug increased PFWD by an average of 1.37-fold or by 48.44 m (95% CI: 35.94 – 60.95 m) [162].
3.1.2.2.3 Sulodexide
It is recommended to use sulodexide (ATC B01AB – heparin group) to increase pain-free walking distance in patients with intermittent claudication [163].
(LEL 1, GOR A)
Comments: sulodexide is a heparinoid group drug (ATC – heparin group), a glycosaminoglycan. The use of sulodexide reduces the likelihood of all-cause and cardiovascular mortality, and also reduces the probability of myocardial infarction [164]. In patients with atherosclerotic peripheral arterial disease combined with diabetes mellitus, the use of sulodexide may have additional benefits [165]. It should be noted that in relevant international consensus documents, this medicinal product is not listed among those recommended for use in patients with intermittent claudication [15, 49, 146].
3.1.2.2.4 Pentoxifylline
It is not recommended to use pentoxifylline** (Anatomical Therapeutic Chemical group C04AD - purine derivatives) to increase pain-free walking distance due to the current lack of reliable data on its effect on intermittent claudication [166].
(Level of Evidence 2, Grade of Recommendation A)
Comments: a drug from the phosphodiesterase inhibitor group (ATC: purine derivatives) — pentoxifylline** — is also used to treat IC [44]. At the same time, according to a meta-analysis of 17 randomized placebo-controlled trials, the quality of the studies was low and their data insufficient to conclude that the drug is effective in increasing walking distance compared with placebo [44, 170].
3.1.2.2.5 Vascular polypeptides
It is recommended to use cattle vessel polypeptides (Anatomical Therapeutic Chemical classification group C05 — angioprotectors) to increase pain-free walking distance in patients with chronic obliterating diseases of the lower extremity arteries of stages I–II according to the Fontaine classification as part of basic therapy [171].
(LEL 2, GOR A)
Comments: the drug exerts a pathogenetic effect and normalizes the function of the vascular wall endothelium. In patients with chronic obliterating diseases of the lower extremity arteries of stage IIB according to the Fontaine-Pokrovsky classification, an increase in pain-free walking distance by 46.2% and ABI by 11.8% has been proven. 95.7% of patients and 94.2% of investigators noted improvement during therapy. The drug prevents the development of atherosclerosis and restores microcirculation in organs and tissues in various diseases and conditions caused by atherosclerotic vascular lesions. It is administered intramuscularly at a dose of 5 mg, once daily, 2 times a week. The course of treatment is 10 injections. The need for repeated courses is determined by the attending physician [171, 172].
3.1.2.2.6 Gene therapy drugs (therapeutic angiogenesis)
It is recommended to perform therapeutic angiogenesis using a genetically engineered biological product encoding VEGF165 growth factor (ATC V03AX other therapeutic products) — plasmid deoxyribonucleic acid [supercoiled circular double-stranded]** — to increase pain-free walking distance in patients with intermittent claudication [173, 174].
(LEL 4, GRC C)
Comment: used as part of complex therapy for patients with chronic lower limb ischemia, as well as in cases where surgical treatment of a patient with CLLI/CLI is impossible due to medical contraindications or is impractical. Recombinant DNA, upon entering the cells of the patient's tissues, stimulates the production of vascular endothelial growth factor, which leads to revascularization in the injection zone. Following two local intramuscular administrations of the drug to patients with lower extremity artery disease of stages IIa–III according to Fontaine-Pokrovsky, PFWD increased by 110%. The therapeutic effect increased over 3 years of follow-up, reaching a 290% increase in PFWD [174].
3.1.2.2.7 Calf blood deproteinized hemoderivative
It is recommended to use deproteinized hemoderivative of calf blood (ATC B06AB – hematological agents) for the symptomatic treatment of peripheral circulatory disorders [175, 176].
(LEL 2, GRR C)
Comments: deproteinized hemoderivative of calf blood restores microcirculation in ischemic tissues and stimulates reparative processes [171].
Qualitative data on the efficacy of the drug in tablet form and over longer treatment periods, as well as on the persistence of the therapeutic effect after completion of the treatment course, cannot be found in the literature. As with sulodexide, in relevant international consensus documents, deproteinized hemoderivative of calf blood is not classified among the drugs recommended for use in patients with IC [15, 49, 146].
3.1.2.2.8 Prostaglandins
It is not recommended to use prostaglandins (ATC - C01EA Prostaglandins) to increase pain-free walking distance in patients with IC due to the current lack of reliable data on their effect on IC [44, 177].
(LEL 1, GOR A)
Comments: the main indication for the prostaglandin group is critical limb ischemia, and the use of these drugs in patients with IC has no advantages over standard conservative treatment regimens and is economically costly [146].
It is recommended to carry out comprehensive conservative therapy for a patient with intermittent claudication (using exercise walking and pharmacotherapy) for at least 3–6 months to assess treatment efficacy, with repeated annual consultations (B01.043.002 Follow-up consultation (examination, inspection) by a cardiovascular surgeon) [44, 175, 176, 177].
(LoE 5, GoR C)
3.2 Surgical treatment (revascularization)
It is recommended to consider surgical treatment of the lower extremities in patients with lifestyle-limiting intermittent claudication when conservative therapy is ineffective or contraindicated, in order to achieve effective revascularization of the affected segment [15, 49, 146, 182, 183, 184, 185, 186, 187, 188].
(LoE 2, GoR B)
Comments: active surgical management should only be pursued if conservative treatments have proven insufficiently effective [15, 49, 146]. The severity of intermittent claudication at which surgical intervention is deemed justified is not clearly defined in the literature. In the Pokrovsky-Fontaine classification, the conventional threshold separating clinically pronounced intermittent claudication from mild intermittent claudication is a pain-free walking distance (PWD) of 200 m [152, 182, 195]. In most studies, this value ranged from 126 to 196 m [152, 182, 184, 196]. However, in a significant portion of publications, the baseline PWD in the surgical group exceeded 200 m [193, 197, 198]. The decision to revascularize the limb of a patient with clinically significant intermittent claudication should be made individually, taking into account the spectrum of comorbidities and the assessment of perioperative complication risks by the attending physician or vascular team.
Aorta and iliac arteries
It is recommended that patients with steno-occlusive lesions of the aorta and iliac arteries undergo arterial reconstruction of the aortoiliac segment using open or endovascular methods (NMU A16.12.050 Endovascular reconstruction of vessel wall; A16.12.038.010 Aortobifemoral bypass grafting). The choice of reconstruction type is determined by members of the vascular team depending on the clinical situation [199, 200, 201, 202].
(LEL 4, GRC C)
3.2.1.1 Open interventions
Historically, the first method for correcting steno-occlusive lesions of the aortoiliac segment is open reconstruction [199, 200]. Its types include unilateral aortofemoral bypass (NMU A16.12.038.012) and aortobifemoral bypass (NMU A16.12.038.010), endarterectomy (NMU A16.12.008) / thromboendarterectomy (NMU A16.12.009) of the aorta, iliac arteries, or occluded synthetic grafts, and various types of extra-anatomic reconstructions (NMU A16.12.038.013 Extra-anatomic bypass) (femorofemoral crossover bypass, axillofemoral bypass, etc.). According to major studies, perioperative mortality ranges from 2.7% to 4.1%, and long-term primary patency at 5 years approaches 90% [200].
Retrospective comparative studies have not revealed statistically significant differences between bypass surgery and endarterectomy [200, 204].
3.2.1.2 Endovascular interventions
It is recommended when performing endovascular reconstruction of the aortoiliac segment (NMU A16.12.050 Endovascular reconstruction of vessel wall) in patients with thrombotic occlusion of the iliac arteries, aortofemoral, iliofemoral, or extra-anatomic bypass graft, to consider using a rotational thrombectomy/atherectomy catheter for effective revascularization of the affected segment [225, 226, 227].
(LEL 4, GRC C)
Comments: mechanical rotational thrombectomy/atherectomy is a relatively new, yet effective and safe method of intravascular revascularization for iliac artery occlusions in acute or subacute thrombosis, chronic lesions, and restenosis following prior angioplasty. All published studies are retrospective and lack a control group; however, they all demonstrated a 100% technical success rate, absence of distal embolization, and zero perioperative mortality. In most cases, the authors supplemented rotational thrombectomy/atherectomy with balloon angioplasty of the iliac artery or peripheral stent implantation [225, 226, 227].
3.2.2 Femoropopliteal segment
3.2.2.1 Common femoral artery
It is recommended for patients with steno-occlusive lesions of the common femoral artery without hemodynamically significant changes in the iliac arteries to consider open endarterectomy (NMU A16.12.008 Endarterectomy) to restore vascular patency [15, 16, 146, 228].
(Level of Evidence 2, Grade of Recommendation B)
Comments: patients with intermittent claudication frequently present with hemodynamically significant lesions of the common femoral artery (CFA) requiring reconstruction [229, 230, 231]. The location of the CFA across the joint articulation of the limb limits the use of implantable devices in this area, which is why CFA lesions have traditionally been considered an indication for open reconstruction—endarterectomy [15, 16, 146]. However, in the presence of contraindications to open surgery, such lesions must be treated via an intravascular approach.
Long-term primary patency after open CFA endarterectomy remains high even after 5–7 years and, according to some data, exceeds 90% [232, 233, 234]. Long-term results of endovascular interventions on the CFA have been scarcely studied over such timeframes.
It is not recommended to perform endovascular correction of common femoral artery lesions in patients with intermittent claudication [228, 237].
(Level of Evidence 2, Grade of Recommendation B)
Comment: in the TECCO study, open intervention was significantly more often accompanied by wound complications and paresthesia, while there were no differences in major complications and mortality. Regarding long-term outcomes (primary patency, freedom from repeat revascularization), the groups did not differ, despite the authors' use of inelastic stainless steel stents [237]. Some teams effectively employ techniques of directed endovascular atherectomy and/or drug-eluting balloons (DEB) for the treatment of steno-occlusive CFA lesions [238, 239, 240].
3.2.2.2 Superficial femoral and popliteal arteries
3.2.2.2.1 Open reconstructions
It is recommended when selecting a conduit for bypass surgery in the femoropopliteal segment (NMU – A16.12.038.006 Femoropopliteal bypass) to prioritize an autologous great saphenous vein graft; if it is absent or unsuitable for use as a conduit, it is recommended to consider using a synthetic blood vessel prosthesis***or semi-closed endarterectomy [238].
(Level of Evidence 3, Grade of Recommendation C)
Comments: the great saphenous vein or a synthetic graft made of polytetrafluoroethylene (PTFE) or Dacron is most commonly used as a conduit [242]. In the early postoperative period after femoropopliteal bypass, mortality reaches 6.7%, the rate of major amputations is 4.2%, and the risk of wound complications is 12.9% [243, 244]. In the long term, outcomes of femoropopliteal bypass are significantly worse in patients with extensive runoff disease involving the calf arteries [246, 247]. An analysis of femoropopliteal bypass outcomes in the UK showed that within 1 year after the intervention, overall mortality is 17.2%, the rate of repeat bypass interventions is 8.5%, and the major limb amputation rate is 10.4% [244].
3.2.2.2.2 Endovascular reconstructions
Endovascular interventions (NMU – A16.12.050 Endovascular reconstruction of vessel wall) are currently the most common method for correcting steno-occlusive lesions of the femoropopliteal segment [185, 259].
The main factors negatively affecting the long-term outcome of endovascular interventions in this area include runoff disease (calf arteries), lesion type (outcomes are worse in the treatment of occlusions and diffuse lesions compared to localized stenosis), degree of arterial calcification, and finally, the stage of ischemia (chronic limb-threatening ischemia or intermittent claudication) [260, 261, 262, 263, 264, 265, 266, 267, 268].
Analysis of vascular registries and retrospective studies does not yield high-quality data to compare the efficacy of open and endovascular approaches to femoropopliteal revascularization in intermittent claudication.
Thus, to date, we do not have a clear understanding of the "threshold" lesion length of the superficial femoral artery and popliteal artery above which endovascular intervention is inferior to open reconstruction in terms of long-term outcomes. Therefore, all currently existing classifications of femoropopliteal segment lesions by severity (TASC, GLASS), as well as the proposed "threshold" lesion length values (TASC II; ESC 2017) upon which authors recommend choosing the revascularization method, are highly conventional [15, 16, 142].
It is recommended to consider balloon angioplasty with or without stent implantation, using drug-eluting peripheral balloons and/or stents, endovascular stent grafts, and endovascular atherectomy/thrombectomy for endovascular reconstruction of the femoropopliteal segment (NMU A16.12.028.001 Mechanical recanalization, balloon angioplasty with stenting of the superficial femoral artery; A16.12.028.002 Mechanical recanalization, balloon angioplasty with stenting of the popliteal artery and major arteries of the leg) [288, 289, 290, 291, 292, 293, 294, 295, 296].
(LoE 2, GoR B)
Comments: in clinical practice, various types of atherectomy—rotational and directional—are effectively used for the treatment of primary lesions of the superficial femoral artery and infrapopliteal bypass grafts, as well as secondary lesions caused by restenosis and atherothrombosis [226, 306, 307, 308, 309, 310]. Laser atherectomy (endovascular vessel wall reconstruction) (LA) is a subtype of endovascular atherectomy. According to a randomized study by Dippel et al. in patients with superficial femoral artery restenosis (mean length 19.6 cm; occlusions 30.5%), LA combined with balloon angioplasty, compared to conventional balloon dilation, provided a higher percentage of technically successful interventions (93.5% vs. 82.7%, p = 0.01), a lower rate of early complications (5.8% vs. 20.5%, p < 0.001), as well as a statistically significant reduction in the risk of repeat revascularizations (by 52%) within 6 months [311].
It is not recommended to perform limb revascularization for lesions of the infrapopliteal segment of the popliteal artery (P3) to restore blood supply to the affected segment in patients with intermittent claudication [308].
(LEL 4, GRC C)
Comments: the study analyzed the outcomes of 34,944 revascularization procedures in patients with intermittent claudication. It was demonstrated that surgical interventions on the infrapopliteal segment are associated with a higher incidence of major and minor amputations (according to multivariate analysis, OR 6.47, 95% CI, 6.45–6.49; P < 0.0001).
3.2.3 Infrapopliteal and inframalleolar segments
It is not recommended to perform revascularization of the tibioperoneal and inframalleolar segments due to an increased risk of adverse outcomes during long-term patient follow-up [312, 313].
(LEL 4, GRC C)
Comments: according to the VQI registry, 22% of bypass procedures for intermittent claudication are performed with the distal anastomosis created at the level of the tibial arteries. At 1 year, primary patency and amputation-free and reintervention-free survival were significantly lower in the femorotibial bypass group compared to the femoropopliteal group (81% vs. 89%; 73% vs. 80%, p < 0.01) [309]. According to the same registry, 3% of endovascular procedures for intermittent claudication are performed at the tibial artery level, and 8% are performed simultaneously at the femoropopliteal and infrapopliteal segments. These interventions were statistically significantly associated with an increased risk of major limb amputation at 1 year (OR 6.47 and 2.32; p < 0.0001) [308].
3.2.4 Approaches to revascularization of multilevel lesions
3.2.4.1 Hybrid revascularization for multilevel lower extremity arterial disease
It is recommended to consider performing hybrid revascularization for multilevel arterial lesions of the limb, including aortoiliac lesions involving the common femoral artery, to effectively restore blood supply to the affected segment and reduce the risk of surgical complications [314, 315].
(LEL 4, GRC C)
Comments: according to the US Nationwide Inpatient Sample (NIS) database, between 2000 and 2004, the number of hybrid interventions performed annually for multilevel steno-occlusive disease of the lower extremity arteries ranged from 2,312 to 2,655, of which 28.3–29.8% were staged procedures (open and endovascular stages performed with an interval of more than 1 day). Various combinations of open and endovascular reconstructions were used, including aortobifemoral bypass, common femoral artery (CFA) endarterectomy, and femorodistal bypass with endovascular correction of inflow or outflow pathways [310].
3.2.4.2 Hybrid interventions for iliofemoral lesions involving the common femoral artery
Рекомендуется hybrid interventions—a combination of open CFA endarterectomy and endovascular correction of the arterial segment above the inguinal ligament when steno-occlusive changes of the aortoiliac segment extend to the common femoral artery (CFA)—for effective revascularization of the affected segment (NOM - A16.12.008.009 Endarterectomy with repair of great vessels) [16, 316, 317, 318].
(LEL 4, GRC C)
Comments: in a randomized trial by Starodoubtsev et al. in patients with iliac artery and CFA lesions, the rate of early postoperative complications was significantly and statistically lower with hybrid reconstruction compared to open revascularization (8.8% vs. 21%, respectively; p=0.03). However, the groups did not differ in terms of primary patency and long-term limb salvage rates [310].
3.3 Limb revascularization for restenosis
It is recommended to consider surgical or endovascular correction of hemodynamically significant restenosis in patients who have previously undergone arterial reconstruction for intermittent claudication to restore effective revascularization of the affected segment [16].
(LoE 5, GoR C)
Comments: one of the indications for reconstructive surgery on limb arteries is the detection of restenosis following prior revascularization [16]. For the treatment of hemodynamically significant restenoses occurring after aortoiliac reconstructions, endovascular surgery methods are currently most frequently used, including simple balloon angioplasty, drug-coated balloon (DCB) angioplasty, cutting balloon catheters, with the implantation of bare-metal peripheral artery stents, as well as peripheral artery endovascular stent-grafts [234, 319, 320, 321].
3.4 Intraoperative imaging during open lower extremity arterial reconstructions
It is recommended to consider intraoperative instrumental visualization of the open arterial reconstruction zone in the lower limb arterial bed (local medical service - A04.11.002 intraoperative ultrasound examination) to detect potential hemodynamically significant changes and their subsequent correction [324].
(Level of Evidence 3, Grade of Recommendation C)
Comments: according to a systematic review by Normahani et al., intraoperative imaging during bypass reconstructions of limb arteries led to the detection of defects requiring revision of the reconstruction in 10-27% of cases. The most common criteria for identifying significant blood flow disturbances during ultrasound scanning were a peak systolic velocity above 180 cm/s or its increase by more than 2.5 times at any segment of the reconstruction, as well as the absence of the diastolic component in the Doppler blood flow spectrum [324].
Secondary prevention and follow-up monitoring after surgical treatment.
Secondary antithrombotic prophylaxis
It is recommended to select the strategy for secondary antithrombotic prevention intraoperatively for intermittent claudication on an individual basis by members of the vascular team or the physician responsible for the patient's treatment, taking into account the specifics of the arterial reconstruction, the presence of contraindications, and limitations to the use of various antithrombotic agents [327].
(LoE 5, GoR C)
Comment: the objective of secondary antithrombotic prevention is to prevent the development of arterial thrombotic complications in the area of arterial reconstruction in the early and late postoperative periods.
Secondary antithrombotic prophylaxis after open arterial reconstructions
Vitamin K antagonists (VKAs)
It is not recommended to routinely use vitamin K antagonists either as monotherapy or in combination with other antithrombotic agents to reduce the risk of repeat revascularization after arterial reconstructions in patients with intermittent claudication [328, 329, 330, 331, 332].
(Level of Evidence 2, Grade of Recommendation B)
Comments: high-quality scientific data on the efficacy of VKAs after open reconstructive interventions for chronic lower limb ischemia are represented by three open-label randomized trials. In two of them, VKAs were used as monotherapy, and target INR values differed significantly from those currently accepted in clinical practice. These circumstances make it difficult to unambiguously interpret the results of these works in terms of practical recommendations [328, 329, 330].
Dual antiplatelet therapy (clopidogrel** + ASA)
It is recommended to prescribe dual antiplatelet therapy with acetylsalicylic acid** (ATC B01AC - platelet aggregation inhibitors excluding heparin) at a dose of 75-100 mg/day and clopidogrel** (ATC B01AC - platelet aggregation inhibitors excluding heparin) at a dose of 75 mg/day following infrainguinal prosthetic bypass surgery for a period of 6 months to 2 years in patients with intermittent claudication to reduce the risk of graft occlusion [333].
(LoE 2, GoR B)
Comments: the double-blind randomized CASPAR trial included patients with chronic lower limb ischemia (intermittent claudication in 33.4%) who underwent infrainguinal bypass reconstructions (autologous vein conduit used in 70.3%). In the prosthetic conduit subgroup, the risk of graft occlusion throughout the entire follow-up period was significantly lower with dual antiplatelet therapy compared to acetylsalicylic acid (RR 0.65; 95% CI 0.45-0.95). The groups did not differ significantly in the frequency of major bleeding complications [333].
Combined oral therapy with acetylsalicylic acid** and a direct factor Xa inhibitor (dual antithrombotic therapy)
It is recommended to use dual antithrombotic therapy with acetylsalicylic acid** (ATC B01AC – platelet aggregation inhibitors, excluding heparin) at a dose of 100 mg/day and rivaroxaban** (ATC B01AF – direct factor Xa inhibitors) at a dose of 2.5 mg twice daily for the secondary prevention of cardiovascular events, major amputations, and acute limb ischemia in patients following lower extremity revascularization for intermittent claudication [330].
(LEL 2, GOR A)
Secondary antithrombotic prophylaxis after endovascular arterial reconstructions
Dual antiplatelet therapy (clopidogrel + ASA)
It is recommended to use dual antiplatelet therapy with acetylsalicylic acid** (ATC B01AC – platelet aggregation inhibitors, excluding heparin) at a dose of 100 mg/day and clopidogrel** (ATC B01AC – platelet aggregation inhibitors, excluding heparin) at a dose of 75 mg/day to reduce the risk of requiring repeat revascularization in patients with intermittent claudication after endovascular interventions on the lower extremity arteries [331].
(LoE 2, GoR B)
Comments: the randomized MIRROR study included patients after endovascular interventions on the femoropopliteal segment who received DAPT or ASA monotherapy for 6 months. Surgery was performed for intermittent claudication in 76.2% of patients. By the end of the follow-up period, the rate of repeat revascularizations of the treated segment (secondary endpoint) for clinical indications was significantly lower with DAPT compared to ASA. In 30% of patients in the DAPT group, resistance to the effect of clopidogrel** was observed due to high residual platelet reactivity [331]. In patients with diabetes mellitus after revascularization, to prevent arterial restenosis, active dynamic monitoring by an endocrinologist and a cardiovascular surgeon is recommended, including duplex ultrasound scanning of the lower extremity arteries every 3 months, along with continuous administration of dual antiplatelet therapy (clopidogrel** + acetylsalicylic acid**) for at least 6 months [332, 333].
Combined oral therapy with acetylsalicylic acid** and a direct factor Xa inhibitor (dual antithrombotic therapy)
It is recommended in patients without a high bleeding risk to consider the use of dual antithrombotic therapy with acetylsalicylic acid** (ATC B01AC – platelet aggregation inhibitors, excluding heparin) at a dose of 100 mg/day and rivaroxaban** (ATC B01AF – direct factor Xa inhibitors) 2.5 mg twice daily combined with short-term administration of clopidogrel** (ATC B01AC – platelet aggregation inhibitors, excluding heparin) for up to 1 month for the secondary prevention of cardiovascular events, repeat interventions, major amputations, and acute limb ischemia in patients after lower extremity endovascular revascularization for intermittent claudication [338].
(LoE 2, GoR B)
Secondary antithrombotic prophylaxis in hybrid arterial reconstructions
An analysis of available publications indicates the absence of any universally accepted antithrombotic therapy regimen in this category of patients. In the study by Zou J. et al., hybrid interventions were performed against the background of dual antiplatelet therapy [339].
There are no high-quality comparative data in the literature regarding the efficacy of various antithrombotic prophylaxis strategies when performing hybrid reconstructions.
Hypolipidemic therapy
It is recommended to prescribe HMG-CoA reductase inhibitors (statins) to reduce all-cause and cardiovascular mortality, as well as to improve limb salvage rates in all patients with intermittent claudication after revascularization surgery [342, 343, 344, 345].
(LEL 4, GRC C)
Comments: moderate- and high-intensity lipid-lowering therapy with statins (rosuvastatin, atorvastatin**) is indicated for all patients with confirmed peripheral arterial atherosclerotic disease to reduce all-cause and cardiovascular mortality [342].
In a retrospective comparative study by Henke et al., statin therapy after infrainguinal bypass surgery significantly increased conduit patency (RR = 3.7; 95% CI 2.1–6.4) and reduced the rate of long-term amputations (RR = 0.34; 95% CI 0.15–0.77) [343].
Use of angioprotectors
It is recommended to prescribe a medication containing bovine vascular polypeptide complex to patients after revascularization surgery to normalize vascular wall endothelial function, prevent the development of atherosclerosis, and restore microcirculation in organs and tissues in atherosclerotic vascular disease, in order to increase pain-free walking distance in adult patients with stage I–II chronic obliterating lower extremity arterial disease according to the Fontaine classification [171, 172, 347].
(LoE 5, GoR C)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
The procedure for developing and implementing an individual rehabilitation and habilitation program is established and carried out in accordance with Order of the Ministry of Labor of Russia No. 466n dated September 18, 2024, "On Approval of the Procedure for Developing and Implementing an Individual Rehabilitation and Habilitation Program for a Disabled Person, an Individual Rehabilitation and Habilitation Program for a Disabled Child and Their Forms, as well as the Procedure for Involving Rehabilitation Organizations in the Development of the Individual Rehabilitation and Habilitation Program for a Disabled Person and the Individual Rehabilitation and Habilitation Program for a Disabled Child, and the Procedure for Coordinating the Implementation of the Individual Rehabilitation and Habilitation Program for a Disabled Person and the Individual Rehabilitation and Habilitation Program for a Disabled Child, Including Monitoring of Such Implementation and Provision of Information on Monitoring Results to the Highest Executive Body of a Constituent Entity of the Russian Federation" (Registered with the Ministry of Justice of Russia on February 4, 2025, No. 81142) [348]. The scope and range of rehabilitation measures for established peripheral arterial disease (PAD) must be strictly regulated, given the high risks of systemic atherosclerosis progression with the development of severe critical limb ischemia associated with high rates of limb loss, morbidity, and mortality [349].
The essence of the rehabilitation program is a set of measures aimed at compensating for lost (impaired) functions and activity limitations. The goal of the program is to prevent the progression of PAD and minimize cardiovascular risk factors. In PAD, these objectives are achieved through behavioral and lifestyle modifications, combined with an additional set of therapeutic and prophylactic non-pharmacological medical measures [350, 351].
It is recommended that physical therapy physicians and physical and rehabilitation medicine physicians promote a culture of mobility and increased physical activity to prevent progression and reduce vascular risk factors in patients with stage I–III PAD (medical service: physical therapy physician examination (consultation); social and rehabilitation work) [352].
(LEL 4, GRC C)
Comments: physical activity (PA) has an inversely proportional effect on cardiovascular morbidity and mortality.
According to Hirsch A.T. et al. (2001), only 18% of patients with intermittent claudication require surgical intervention and 10% are candidates for amputation over a 10-year follow-up period, while mortality from myocardial infarction and stroke in patients with PAD at 5, 10, and 15 years can reach 30%, 50%, and 70%, respectively [350].
The World Health Organization (WHO) recommends 150 minutes per week of moderate-intensity physical activity (brisk walking (2.4 to 4 mph), cycling (5 to 9 mph), active yoga, and recreational swimming) or 75 minutes per week of high-intensity physical activity (jogging, cycling (>10 mph), playing tennis, swimming) to reduce the risk of cardiovascular diseases [346].
It is recommended to prescribe an individualized exercise program under the supervision of an instructor or exercise therapy physician for patients with intermittent claudication to improve functional status and quality of life, as well as to enhance walking capacity or improve collateral circulation in the limbs [159, 355, 356, 357, 358].
(LEL 1, GOR A)
Comments: supervised treadmill walking (medical services: terrain therapy (walking therapy); exercise therapy using exercise equipment) is the most effective form of rehabilitation for patients with intermittent claudication and should last 30 to 60 minutes, conducted 3 times a week for at least 3 months. The suggested belt speed is 3.2 km/h with an increasing treadmill inclination angle. At the same time, maximizing ischemic muscle pain during walking should always be avoided [360].
A Cochrane systematic review (2017), including 32 randomized controlled trials (n=1835) investigating the efficacy of physical exercise compared with control or drug therapy in patients with intermittent claudication due to PAD, provides high-quality evidence that exercise programs significantly improve both pain-free walking distance and maximum walking distance in patients with intermittent claudication. Physical exercise may improve quality of life compared with placebo or standard care [159].
It is recommended to use balneotherapy in the rehabilitation of patients with PAD to reduce the symptoms of IC, including 3 months after reconstructive surgery and 8 weeks after endovascular interventions, to improve microcirculation in the surgical area [366, 367].
(LoE 5, GoR C)
Comments: balneotherapy (BT) includes various therapeutic procedures using mineral water (chloride-sodium, carbon dioxide, hydrogen sulfide, iodine-bromine, and radon mineral baths) (Medical Service Code [MSC] - therapeutic mud application for peripheral vascular diseases, therapeutic mineral baths, therapeutic hydrogen sulfide baths, therapeutic radon baths, therapeutic gas baths).
The therapeutic effect of mineral baths is due to the mechanical, chemical, and thermal effects of thermal water on the skin receptors of the extremities, dilation of capillaries and precapillaries, improved microcirculation, increased blood flow velocity, and decreased peripheral resistance [366, 367]. It is recommended to use physiotherapeutic methods in the rehabilitation of patients with PAD with Fontaine stage IIa/b limb ischemia to develop collateral circulation, reduce pain, and improve the functional state of the limb [356, 370, 371].
(LoE 5, GoR C)
Comment: physiotherapy methods are aimed at preserving or reactivating active and passive mechanisms of lower limb blood flow regulation. Vasodilation is achieved through the use of physiotherapeutic techniques such as magnetotherapy (MSC general magnetotherapy, exposure to magnetic fields), galvanic current, iontophoresis, Bernard's diadynamic currents (MSC Bernard's currents for diseases of the peripheral nervous system), TENS, and interference currents (MSC exposure to interference currents) [370].
The use of calf muscle electrical stimulation demonstrates an increase in walking distance and a reduction of pain in patients with PAD and intermittent claudication [373, 374, 375, 376].
It is recommended to use enhanced external counterpulsation (MSC External counterpulsation) in the rehabilitation of patients with PAD and Fontaine stage IIb IC to improve endothelial function and increase walking duration [377, 378].
(LEL 4, GRC C)
Comment: it has been established that EECP with individual pressure not exceeding 160 mm Hg, set according to Doppler flow parameters during counterpulsation (individual shear rate diagnostics), enhances peripheral perfusion in Fontaine stage IIb PAD [377].
A study by Brix M. et al., 2017 showed that the use of long-term EECP (5 weeks) leads to a significant increase in the plasma nitric oxide level in patients and the expression of related molecular markers in peripheral blood mononuclear cells (PBMCs) [378].
It is recommended to use pulsed magnetotherapy (MSC – General magnetotherapy) and low-intensity laser therapy (MSC – Exposure to low-intensity laser radiation in diseases of major blood vessels) in the rehabilitation of patients with stage I-II PAD and IC to improve the functional state of the limb [379].
(LEL 2, GRR C)
5. Prevention and Dispensary Observation
5.2 Dispensary monitoring
It is recommended that patients after lower limb revascularization for IC undergo follow-up examinations and consultations with a cardiovascular surgeon (MSC - Follow-up visit (examination, consultation) of a cardiovascular surgeon), clinical examination, and/or lower limb arterial ultrasound Dopplerography to monitor limb status, assess the function of the performed arterial reconstruction, and detect signs of restenosis and clinical recurrence of limb ischemia [384, 385, 386, 387, 388].
(LoE 2, GoR B)
Comments: follow-up examinations for dynamic monitoring of the patient's condition are performed by a cardiovascular surgeon twice a year (MSC follow-up visit (examination, consultation) of a cardiovascular surgeon). The first examination of patients after surgeries is performed 2–4 weeks after discharge from the hospital; clinical examination in the postoperative period is performed once a year.
The risk of restenosis and reocclusion after revascularization for IC requires follow-up dispensary monitoring of the limb status and the function of the performed arterial reconstruction. This monitoring may include periodic clinical examination and/or duplex ultrasound scanning (DUS).
6. Organization of Medical Care
Indications for planned hospitalization in a medical organization for patients with IC:
performance of surgical or endovascular treatment of lower limb arteries,
surgical or endovascular treatment of conditions and complications following
open and endovascular interventions on lower limb arteries.
Indications for discharging a patient with IC from a medical organization:
completed surgical or endovascular treatment of lower limb arterial diseases.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance evaluation (yes/no) |
|---|---|---|
1. | Collection of complaints and medical history was performed | Yes/no |
2. | Physical examination was performed | Yes/no |
3. | Assessment of the local status of the limb was performed | Yes/no |
4. | A complete (clinical) extended blood count, general therapeutic blood biochemistry analysis (assessment of blood creatinine and urea levels, ALT and AST activity, blood sodium, potassium, total bilirubin, and glucose levels, and serum C-reactive protein) were performed. | Yes/no |
5. | Lower extremity arterial duplex ultrasonography was performed. | Yes/no |
6. | Non-invasive arterial studies were performed (duplex scanning, CTA, MRA). | Yes/no |
7. | Invasive arterial studies (angiography) were performed in the absence of non-invasive studies and when revascularization procedures were planned. | Yes/no |
8. | Pharmacotherapy was prescribed and recommendations were provided to reduce the risk of cardiovascular events. | Yes/no |
9. | Supervised or independent exercise therapy (walking) was recommended as the first-line treatment for intermittent claudication. | Yes/no |
10. | Pharmacotherapy was prescribed to increase pain-free walking distance. | Yes/no |
11. | Lower extremity revascularization was performed in patients with intermittent claudication when conservative therapy was ineffective for 3–6 months, or if contraindications to conservative therapy were present. | Yes/no |
12. | Pharmacotherapy was prescribed and recommendations were provided to reduce the risk of arterial graft/stent occlusion. | Yes/no |
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Appendix A1. Working Group Composition
Belov Yuri Vladimirovich - MD, PhD, Professor, Academician of the Russian Academy of Sciences, Director of the Institute of Cardio-Aortic Surgery at the Petrovsky National Research Centre of Surgery. President of the Russian Society of Angiologists and Vascular Surgeons.
Bredikhin Roman Aleksandrovich - MD, PhD, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons, Member of the Executive Council of the Phlebology Association of Russia, Member of the Russian Society of Surgeons.
Gavrilenko Aleksandr Vasilyevich - MD, PhD, Professor, Academician of the Russian Academy of Sciences, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons.
Zatevakhin Igor Ivanovich - MD, PhD, Academician of the Russian Academy of Sciences, Professor, Honorary President of the Russian Society of Surgeons, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons.
Kalinin Roman Evgenyevich - MD, PhD, Professor, Member of the Board of the Russian Society of Angiologists and Vascular Surgeons, Member of the Executive Council of the Phlebology Association of Russia, Member of the Russian Society of Surgeons, Association of Cardiovascular Surgeons of Russia, Head of the Department of Cardiovascular, Endovascular Surgery and Radiology at the Ryazan State Medical University of the Russian Ministry of Health.
Kuryanov Pavel Sergeevich - PhD, Head of the Department of X-ray Surgical Diagnostic and Treatment Methods at St. George City Hospital, Head of the Diabetic Foot and Surgical Infection Center, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons.
Matyushkin Andrey Valeryevich - MD, PhD, Professor, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons.
Sapelkin Sergey Viktorovich - MD, PhD, Chief Researcher at the Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Health, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons, Member of the Executive Council of the Phlebology Association of Russia, Member of the Russian Society of Surgeons.
Svetlikov Aleksey Vladimirovich - MD, PhD, Professor at the Department of Hospital Surgery, Saint Petersburg State University, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons.
Sokurenko German Yuryevich - MD, PhD, Professor, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons, St. Petersburg.
Suchkov Igor Aleksandrovich - MD, PhD, Professor, Vice-President of the Russian Society of Angiologists and Vascular Surgeons, President of the Phlebology Association of Russia, Member of the Board of the Russian Society of Surgeons, Professor at the Department of Cardiovascular, Endovascular Surgery and Radiology at the Ryazan State Medical University of the Russian Ministry of Health, Member of the Association of Cardiovascular Surgeons of Russia.
Fokin Aleksey Anatolyevich - MD, PhD, Professor, Member of the Presidium of the Russian Society of Angiologists and Vascular Surgeons, Head of the Department of Surgery at the Institute of Continuing Professional Education of the South Ural State Medical University of the Russian Ministry of Health.
Chupin Andrey Valeryevich - MD, PhD, Professor, Vice-President of the Russian Society of Angiologists and Vascular Surgeons, Head of the Department of Vascular Surgery at the Vishnevsky National Medical Research Center of Surgery of the Russian Ministry of Health, Moscow.
Conflict of interest: all members of the Working Group confirmed the absence of financial support/conflict of interest that needs to be reported.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines: specialists with higher medical education in cardiovascular surgery, cardiology.
These guidelines were developed in accordance with:
- Order No. 103n of the Ministry of Health of the Russian Federation dated May 8, 2019;
- Methodological recommendations for assessing the scientific validity of information included in clinical guidelines (Center for Expertise and Quality Control of Medical Care of the Ministry of Health of the Russian Federation, 2019). These guidelines are based on the main principle of evidence-based medicine, according to which decisions on the use of specific medical technologies must be based on a comprehensive analysis of all available scientific evidence of their efficacy and safety, rather than on expert opinion and the personal clinical experience of physicians.
Assessment of the scientific validity of information included in clinical guidelines (CG) is carried out by assessing the levels of evidence (LE) and grades of recommendation (GR) of thesis recommendations (Tables 1, 2, 3).
Table 1 Scale for assessing levels of evidence (LE) for diagnostic interventions
LoE | Hierarchy of clinical study designs in descending order of the level of evidence from 1 to 5 |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized clinical trials with meta-analysis |
2 | Individual studies with reference-method control, or individual randomized controlled trials and systematic reviews of studies of any design except randomized controlled trials incorporating meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2 Scale for assessing levels of evidence (LE) for methods of prevention, treatment, and medical rehabilitation, including those based on the use of natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)
LoE | Hierarchy of clinical study designs in descending order of the level of evidence from 1 to 5 |
|---|---|
1 | Systematic review of randomized controlled trials with meta-analysis |
2 | Individual randomized clinical trials and systematic reviews of studies of any design, excluding randomized clinical trials, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3 Scale for assessing grades of recommendation (GR) for methods of prevention, diagnosis, treatment, and medical rehabilitation, including those based on the use of natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
Table 4. Classifications of the severity of chronic lower limb ischemia
Intermittent claudication | Classification Fontaine A.V. Pokrovsky Rutherford Stage Category | |||
|---|---|---|---|---|
Asymptomatic | I | I | 0 | 0 |
Mild IC | IIa | IIa (200-1000 m) | I | 1 |
Moderate IC | IIb | IIb (<200 m) | I | 2 |
Severe IC | III | I | 3 | |
Rest pain | III | II | 4 | |
Initial trophic changes | IV | IV | III | 5 |
Ulcer or gangrene | IV | 6 | ||
Appendix B. Physician Action Algorithms
Decision-making algorithm for the treatment of a patient with symptoms of intermittent claudication.
Appendix C. Patient Information
Intermittent claudication (IC) – pain or discomfort in the lower extremity muscles (most often in the calf, less often in the buttock, thigh, or foot) that occurs during physical exertion and subsides after a few minutes of rest. Sometimes, for example, against the background of diabetes mellitus or severe heart failure, classical symptoms of intermittent claudication may be absent, but discomfort in the limb is noted, which does not go away immediately during rest.
The pain is caused by the fact that working muscles do not receive sufficient oxygen due to the narrowing of the arterial vessel supplying this area. Lactic acid and metabolic products accumulate in the tissues, and a burning sensation and pain appear. After a short rest, when the muscle is relaxed, blood flow is restored and oxygen transport again supports the metabolism of the muscle tissue.
Most often, peripheral arterial obstruction is caused by atherosclerosis, a chronic disease characterized by the gradual formation of "plaques." These vascular wall thickenings can narrow (cause obliteration) or completely block the vessel lumen, impairing blood transport to tissues. Atherosclerosis is a systemic disease, meaning it can affect any arteries in the body. Therefore, it should be kept in mind that when intermittent claudication (IC) appears, the condition of the cardiac arteries, carotid arteries, and aorta must also be evaluated.
The risk of lower extremity artery disease increases with age. Men are affected somewhat more frequently than women. The main factors in the development of the disease include smoking (which increases the risk of IC by 3–10 times), diabetes mellitus, lipid metabolism disorders, arterial hypertension, and increased blood viscosity.
Manifestations of the disease can vary among individuals and at different stages of the condition. There may be a prolonged asymptomatic period, followed by gait impairment, trophic disorders (long-healing ulcers even after minor skin trauma), rest pain, necrosis, and gangrene (tissue death).
A cardiovascular surgeon can assess the degree of blood flow impairment in a lower extremity artery during the physical examination. This involves evaluating the condition of the skin and leg muscles, vascular pulsations, and comparing blood pressure in the arm and leg (ankle-brachial index). For a more precise localization of the arterial lesion level and the selection of further treatment tactics, additional diagnostic methods may be prescribed, such as ultrasound techniques, computed tomography, or magnetic resonance imaging.
Timely and comprehensive treatment of lower extremity artery disease can not only reduce the severity of intermittent claudication but also significantly decrease the risks of severe cardiovascular complications (myocardial infarction and stroke). Start with lifestyle modifications! This way, you can influence the main risk factors of the disease.
Smoking cessation is a mandatory measure! Inhalation of tobacco smoke components causes blood vessels to constrict, reduces blood oxygen levels, increases heart rate and blood pressure, which further worsens circulatory conditions in the limb.
Regular physical activity is the cornerstone of treatment for intermittent claudication. Walking stimulates the formation of collateral vessels, which ensure blood flow bypassing the narrowed arterial segment. Regular training helps not only to reduce pain but also to improve the condition of the cardiovascular system, decrease the need for surgery, maintain a normal weight, and boost mood. 30–60 minute walks are recommended at least 3–5 times a week. Walk at a speed you can comfortably maintain for 3–10 minutes. Continue moving until near-maximal pain occurs—this pain cannot cause damage (the presence of a foot ulcer may require limiting the load on that leg and an additional specialist consultation). Take a break to rest until the pain disappears and resume walking. Gradually increase your speed and walking distance. Usually, a few weeks of training are required to reduce symptoms. To maintain your quality of life, make daily active one-hour walks a lifestyle habit.
Healthy nutrition will help lower cholesterol and blood sugar levels and normalize weight. We obtain about 20% of all cholesterol from food, and dietary correction allows us to influence this 20%. Eating 4–5 small meals a day without overeating is recommended. Avoid fatty foods. Pork, lamb, goose, duck, offal, processed meats (sausages, frankfurters, smoked meats), fatty river fish, high-fat dairy products (butter, cheese, sour cream), margarine, egg yolk, and confectionery are particularly rich in "bad" cholesterol. The diet should be based on lean meats (lean beef, chicken, turkey), lean fish or fatty marine fish (high in omega-3 polyunsaturated fatty acids, which help reduce the formation of atherosclerotic plaques), vegetable oils (sunflower, olive, flaxseed), legumes, bread, vegetables (carrots, beets, cabbage, broccoli, pumpkin, eggplant, onions, garlic), and fruits (citrus fruits, plums, pears, apples, black currants, bananas). Try to avoid fried foods, preferring boiled, stewed, or baked options. Reduce the amount of salt and sugars consumed. Drink sufficient fluids (at least 1 liter per day); exclude sugary drinks, alcohol, and sweet juices.
Body weight control is very important. Overweight and obesity are additional risk factors for many diseases, including lower extremity arterial disease. It is recommended to target a body mass index (BMI) of less than 25 (BMI = body weight (kg) / height2 (m)).
Pharmacotherapy is prescribed to control cholesterol, blood pressure, glucose levels, and blood viscosity. Do not forget to report all medications you are already taking or have been prescribed!
Surgical treatment may be required if conservative treatment has low efficacy, often at more advanced stages of the disease. The vascular surgeon assesses the need for surgery and the treatment method. Currently, minimally invasive interventions (endovascular procedures), such as balloon angioplasty or stenting, are performed more frequently. In certain situations, placement of vascular grafts or bypass surgeries—which create blood flow bypassing the occluded artery—may be required. It must be remembered that even after surgery, it is necessary to continue taking prescribed medications, undergo regular medical check-ups, and adhere to healthy lifestyle recommendations to prevent or timely detect signs of disease progression.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Not required.