Varicose veins of the lower extremities: clinical guidelines

List of Abbreviations

ASVAL – Ablation Selective des Varices sous Anesthesie Locale

CEAP – classification of chronic venous disorders (Clinical, Etiological, Anatomical, Pathophysiological)

CHIVA – Cure Conservatrice et Hemodynamique de l’Insuffisance Veineuse en Ambulatoiere

EFE – endovenous fluence equivalent

UIP – International Union of Phlebology

ATC – Anatomical Therapeutic Chemical classification

ARF – Russian Phlebological Association

FV – femoral vein

GSV – great saphenous vein

VAD – venoactive drugs

VAS – visual analog scale

LEVD – lower extremity varicose veins

IVUS – intravascular ultrasound

VTE – venous thromboembolism

SRLD – State Register of Medicinal Products

CI – confidence interval

DUSLS – duplex ultrasound scanning of lower extremity veins

CIT – cyanoacrylate-induced thrombosis

LEP – linear endovenous energy density

ICD-10 – International Statistical Classification of Diseases and Related Health Problems 10th Revision

MPFF – micronized purified flavonoid fraction (in ATC: Purified micronized flavonoid fraction (diosmin + flavonoids calculated as hesperidin))

SSV – small saphenous vein

MSE – medical and social expertise

MSCT – multislice computed tomography

MECC – medical elastic compression garments (A15.12.002 Lower extremity elastic compression)

MOCA – mechanochemical ablation

IVC – inferior vena cava

NSAIDs – nonsteroidal anti-inflammatory and antirheumatic drugs (ATC: M01A, Nonsteroidal anti-inflammatory and antirheumatic products)

NTND – non-thermal non-tumescent techniques

CFV – common femoral vein

PV – perforating veins

PoV – popliteal vein

PTS – post-thrombotic syndrome

RV – reticular veins

RCTs – randomized controlled trials

RFA – radiofrequency ablation

RF – Russian Federation

SPJ – saphenopopliteal junction

SFJ – saphenofemoral junction

TA – telangiectasias

DVT – deep vein thrombosis

EHIT – endovenous heat-induced thrombosis (synonym: endovenous thermally induced thrombosis, ETIT)

SVT – superficial vein thrombosis (thrombophlebitis)

PE – pulmonary embolism

UL – venous leg ulcer

VADs – venoactive drugs

CVI – chronic venous insufficiency

CVD – chronic venous diseases

CAVA – cyanoacrylate vein ablation

EVLA – endovenous laser ablation

Terms and Definitions

Atrophie blanche – a small, rounded patch of skin, white (pale) in color, usually located within an area of hyperpigmentation. It is regarded as a pre-ulcerative condition.

Comment. Pale scars at the site of healed ulcers are not classified as atrophie blanche.

Lower extremity varicose veins (LEVV) – a disease characterized by primary varicose transformation of superficial veins.

Varicose superficial veins – subcutaneous dilated veins with a diameter greater than 3 mm in the standing position. They typically have a nodular (saccular) and/or tortuous (serpentine) appearance.

Venous leg ulcer – a defect of the skin and soft tissues within an area of trophic disorders caused by chronic venous disease.

Venous eczema (stasis dermatitis, eczema-like dermatitis) – a type of eczema resulting from chronic venous insufficiency, most frequently localized on the lower extremities and characterized by serous inflammation of the dermal papillae and focal spongiosis of the epidermis, manifesting as a polymorphic pruritic rash (vesicles, papules, erythema, etc.).

Venous edema – enlargement of a limb caused by an increase in fluid volume in the skin, subcutaneous tissue, and interfascial space, often accompanied by characteristic pitting upon digital pressure, caused by chronic venous insufficiency.

Venous reflux – impairment of the venous valve system resulting in retrograde blood flow through the superficial and/or deep venous system of the extremity, as well as the perforating vein system.

Hyperpigmentation – discoloration of the skin consisting of brown spots of varying size and varying intensity. Hyperpigmentation secondary to CVI is most commonly localized in the lower third of the leg on the medial surface, but may spread to other segments of the leg and the foot.

Duplex scanning – a method of ultrasonic vascular examination in which, if necessary, two or three scanning modes can be used simultaneously. It is a type of ultrasonic angioscanning. A04.12.006.002 Duplex scanning of lower extremity veins.

Glue-induced thrombosis (glue-induced thrombosis (GIT), endovenous glue-induced thrombosis, EGIT) – partial or complete occlusion of a deep vein or prolapse of adhesive material into a deep vein following glue ablation of a superficial vein.

Crossectomy (Trendelenburg operation) – high ligation (directly at the deep axial vein) of the greater (or lesser) saphenous vein with mandatory ligation of all saphenofemoral/saphenopopliteal tributaries and excision of the superficial vein trunk within the surgical wound.

Lipodermatosclerosis – induration (fibrosis, sclerosis) of the skin and subcutaneous tissue, most commonly localized in the lower third of the leg on the medial surface.

Objective symptoms of chronic venous disorders – visible manifestations of venous diseases, namely: dilated veins, telangiectasias (TA), reticular veins (RV), varicose veins, lower leg edema, skin and subcutaneous tissue changes, venous leg ulcers.

Open surgical intervention – open surgery involving high junctional division and ligation of the greater or lesser saphenous veins with their subsequent removal (stripping). Combined with the removal of varicose tributaries, the operation is sometimes referred to as "combined phlebectomy".

Foam (microfoam, foam-form) sclerotherapy – a method of sclerobliteration using a sclerosing agent in the form of microfoam prepared manually, using automated devices, or industrially from a liquid preparation and air or a special gas (gas mixture).

Reticular veins – dilated and tortuous subcutaneous veins 1–3 mm in diameter.

Recurrence of lower extremity varicose veins – the appearance of varicose veins after a completed course of invasive treatment.

Stripping – removal of the greater or lesser saphenous vein trunk using a specialized probe.

Subjective symptoms of chronic venous disorders – complaints caused by venous disease or functional overload of the venous system, namely: pain, feeling of heaviness and fullness, tingling, burning, itching, muscle cramps, pulsation, leg fatigue and tiredness, restless legs syndrome. These symptoms are not pathognomonic.

Telangiectasias (spider veins) – dilated intradermal veins less than 1 mm in diameter.

Thermal-induced thrombosis (thermally induced thrombosis (TIT), endovenous thermally induced thrombosis (ETIT), endovenous heat-induced thrombosis (EHIT)) – partial or complete obstruction of a deep vein or prolapse into a deep vein of masses directly connected with masses formed in the superficial vein as a result of its thermal ablation.

Tumescent anesthesia – a type of local anesthesia using significant volumes of a low-concentration local anesthetic. In CVD surgery, tumescent anesthesia consists in creating a "cuff" of anesthetic solution around the subcutaneous veins.

Venoactive drugs (venotonic drugs, phlebotropics, veno-active medications) – groups of biologically active substances united by the ability to increase venous tone and reduce the severity of vein-specific symptoms and syndromes (ATC: C05B, C05CA, C05CX, B01AB).

Chronic venous insufficiency – a pathological condition caused by impaired venous outflow, manifesting as moderate or severe edema, skin and subcutaneous tissue changes, and trophic ulcers (Classes C3–C6 according to CEAP).

Chronic venous diseases – all morphological and functional disorders of the venous system. The main nosological forms of CVD are lower extremity varicose veins (LEVV), pelvic varicose veins, post-thrombotic syndrome (PTS) of the lower extremities, angiodysplasias (phlebodysplasias), telangiectasias and reticular veins, and phlebopathies.

Comment. Veins visible through the skin in fair-skinned individuals (enhanced venous pattern) should not be considered pathologically altered.

Endovenous thermal ablation (endoluminal thermal ablation) – a group of methods for eliminating pathological reflux through intravascular thermal action on a vein with its subsequent obliteration and fibrous transformation. The main methods of endovenous thermal ablation are laser and radiofrequency.

Corona phlebectatica (phlebectatic corona, venous foot corona) – a dense fan-shaped network consisting of multiple small intradermal veins less than 3 mm in diameter in the medial and/or lateral ankle region and submalleolar foot area. It includes the following components: blue telangiectasias (deep venules), red telangiectasias (superficial venules), flare patches (capillaries), and venous cups (subcutaneous veins).

Comment. Corona phlebectatica should not be confused with telangiectasias of the dorsum of the foot in skin atrophy in patients receiving long-term corticosteroids, nor with chronic atrophic Herxheimer dermatitis (a late manifestation of Lyme disease).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Lower extremity varicose veins – a chronic disease with primary varicose dilatation of the subcutaneous veins of the lower extremities, which can lead to the development of chronic venous insufficiency (edema, hyperpigmentation, venous eczema, lipodermatosclerosis, trophic ulcer).

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

Etiology

The high detection rate of CVD indicates a significant role of heredity in the nature of this disease. It is known that the risk of varicose vein development in children reaches 90% when both parents suffer from the disease, 25% for boys and 62% for girls when one parent has the pathology, and 20% when both parents are healthy [1]. Precise understanding of the genetic basis of CVD development is lacking, but in recent years active study of this aspect of the problem has begun, primarily in patients with LEVV [2–4].

The FOXC2 gene encodes a transcription factor required for the development of venous and lymphatic vessels during embryonic and postnatal periods [5–8]. Playing an important role in the formation of venous valves, FOXC2 mutations can cause superficial and deep venous valve insufficiency [9,10]. Upregulation of FOXC2 expression is observed in the development of venous hypertension, which entails an increased synthesis of mRNA for the endothelial marker Dll4 (Delta-like ligand 4), associated with the secretion of the Hey2 protein [8,11]. Induction of the FOXC2-Dll4-Hey2 pathway activates smooth muscle cell proliferation and venous wall remodeling in patients with varicose veins. A study conducted on biological material obtained from our country's population presents data indicating the potential significance of specific haplotypes (rs7189489 C–rs4633732 T–rs34221221 C–rs1035550 C– rs34152738 T–rs12711457 G) in the development of varicose veins [12].

The MCP1 gene encodes the synthesis of monocyte chemoattractant protein 1 [13]. The main function of MCP1 is to attract monocytes, basophils, and T lymphocytes to the area of inflammation [14]. The MCP1 protein is capable of stimulating smooth muscle cell proliferation in the venous wall [11]. It has been shown that the homozygous G/G genotype is associated with clinical class C2, early manifestation (under 30 years of age) of varicose veins, and is detected in patients without an obvious family history of the disease [14]. It cannot be ruled out that this gene plays a greater role in the initiation of the disease rather than in its progression.

In European populations, a higher incidence of venous trophic ulcers was shown in carriers of the rs1800562A allele of the hemochromatosis gene HFE p.C282Y [15]. A domestic study did not find a significant association between the presence of this HFE p.C282Y allele and the incidence of trophic ulcers, although it was more frequently detected in patients with varicose veins. Conversely, this association was traced to another HFE allele, p.H63D (rs1799945), which is absent in Europeans [16].

Other most studied genes potentially responsible for the initiation or development of chronic venous diseases and their complications include MMPs/TIMPs, COL1A2, VEGF, and Procollagen. COL1A2, HSP90, ILK, MGP, Oct-1, TGF-α1, Type I and III collagen, VEGF-A, and VEGF-R are widely studied in the pathogenesis of varicose veins, along with COL1A2, a-FGF, FGF-R, BAT1, ER-b, FPN1, IL-1, MTHFR, Procollagen, TNF-α. The role of the VEGF gene in the development of chronic venous insufficiency has already been demonstrated in a number of studies [4].

The etiology of such primary chronic venous diseases as phlebodysplasias, reticular veins, and telangiectasias remains poorly understood.

Pathogenesis

The pathogenesis of chronic venous disease is a complex and multifactorial process. Currently, the following concepts regarding the mechanisms of damage to the venous wall and valves in varicose veins have been established. Alterations in blood flow patterns developing in the veins of the lower extremities lead to changes in "shear stress", i.e., the mechanical stress on the endothelial cell membrane arising in response to its displacement by laminar blood flow. Due to venous stasis, areas with low or zero shear stress form on the endothelial surface, which inevitably affects the functional activity of the cells [15–18]. In particular, multidirectional shear stress resulting from retrograde blood flow can trigger the appearance of inflammatory and thrombogenic endothelial phenotypes, which acquire the ability to bind blood cells (leukocytes, platelets) and protein molecules on their surface [19,20].

A significant role in the pathogenesis of varicose vein transformation is played specifically by the rolling, adhesion, and activation of leukocytes on the surface of morphologically intact but dysfunctional endothelium. Data accumulated in recent years indicate that the remodeling of the venous wall and venous valves is driven by a specific inflammatory process [16,21–26]. This premise is supported by the finding that varicose dilatation is accompanied by infiltration of the venous wall and valve cusps by monocytes and macrophages. Moreover, cellular infiltrates form in areas of the venous wall where endothelial cells produce cell adhesion molecules [6,15,21,23].

Proteolytic enzymes, particularly matrix metalloproteinases synthesized by endothelial cells and macrophages, induce the degradation of proteins forming the extracellular matrix of the venous wall [6,27–29]. The cascade of inflammatory changes, accompanied by the production of inflammatory mediators and growth factors, leads to the transformation of the venous wall and valves [6,24]. It should be noted that all pathological processes initiated by leukocyte-endothelial interactions are highly complex and not yet fully understood.

All elements of the venous wall are involved in the pathological process of chronic lower limb venous disease [30–32]. In the tunica intima, the endothelium is the first to suffer, being directly exposed to the adverse effects of abnormal venous outflow. Light and electron microscopy reveal alterations in endothelial cells and their structural arrangement, up to the complete destruction of the endothelial lining [33,34]. Overall, in the early stages of the disease, intimal thickening is detected in varicose veins [6,30,34]. This is caused by changes in the subendothelial layer, characterized by an increased content of elastic and collagen fibers, migration of muscle cells into the subendothelium, against the background of dystrophic changes of the mucoid and fibrinoid inflammation type [31,34]. In later stages, fibrosis of the inner lining of the veins develops, elastic fibers thicken, and the internal elastic membrane becomes loose and degraded [30,33,35].

In the tunica media, hypertrophy of muscular elements is observed in the early stages of the disease [18,30,31,36], leading to its marked thickening.

As the pathological process progresses, atrophy of the muscular structures develops in the tunica media, causing it to thin. It is common to observe alternating areas of the wall with hypertrophy and atrophy of muscular elements [6,22]. Furthermore, immunohistochemical and electron microscopic studies have shown that there is not merely a reduction of muscular structures in the wall, but also a shift in the role of muscle cells from contractile to synthetic, proliferative, and phagocytic [6,34,37], as evidenced by cytoplasmic vacuolization and a moderate number of mitochondria [34]. The identified changes confirm that not only structural but also functional remodeling of smooth muscle cells occurs in the venous wall. Such functional changes underlie the remodeling of the vessel wall [35,37].

Simultaneously, changes in the content of elastic and collagen fibers are detected in the tunica media [31,33,34,36,38–40]. Their amount increases. In later stages, destruction of elastic fibers and elastolysis are observed. Frequently, only fragments of elastic fibers are detected [34,41]. Similar alterations of elastic fibers are noted in the tunica adventitia [36,39]. The reduction in elastin synthesis and the destruction of elastic fibers also make a substantial contribution to the deterioration of the elastic and resilient properties of the venous wall [18,36,39].

An important factor in the pathogenesis of varicose transformation of superficial veins in chronic lower limb venous disease is the dysregulation of collagen synthesis [19,41,42]. Numerous studies have established multifaceted changes in the content of various collagen types within the venous wall. Researchers have focused primarily on investigating the content of interstitial type I and III collagens, which form large fibrils in the venous wall. General changes in collagen fibers in the wall of varicose veins have been described in a number of works. The identified abnormalities can be characterized as disorganization of collagen fibers [35,41]. Their number increases [42,43], but at the same time they lose their normal structure, can become thickened and coarse or thinner [34], and frequently acquire bizarre shapes [44].

Most authors note a shift in the ratio of the two collagen types toward an increase in type I collagen and a decrease in type III collagen within the wall [19,39,41,45]. The dysregulation of collagen synthesis impairs the elastic and resilient properties of the venous wall, creating conditions for its varicose transformation.

Overall, the developing pathological changes in superficial veins in chronic lower limb varicose veins can be characterized as a progressive increase in the atrophy of muscle elements, a decrease in elastic fibers, and an increase in collagen fiber content. This causes alterations in the elastic and mechanical properties of the venous wall and the varicose transformation of superficial veins. Despite a more complex structural and functional organization, valves are a modified part of the venous wall, formed by the same fibers and cells, and therefore should undergo similar pathomorphological changes. Most likely, structural remodeling in the valves occurs synchronously with changes in the wall. It should be noted that no correlation has been identified between the nature of pathomorphological changes developing in the venous wall and the clinical severity of the disease, nor with the degree of reflux in the proximal segment of the great saphenous vein [46].

The mechanism of "leukocyte-driven aggression" is considered crucial in the development of trophic disorders in chronic venous disease (CVD). Under the influence of venous hypertension and stasis, extravasation of macromolecules (fibrinogen and $\alpha_2$-macroglobulin) and erythrocytes into the interstitial tissues occurs [6]. Their degradation products possess a potent chemotactic effect and serve as a signal for the recruitment and activation of leukocytes [22]. Concurrently, the expression of the ICAM-1 cell adhesion molecules increases on endothelial cells of the microvasculature, which is utilized by macrophages, lymphocytes, and mast cells for diapedesis through the intact endothelium of capillaries and postcapillary venules into the interstitium [6, 20, 43].

Activated leukocytes, migrating into surrounding tissues, stimulate the synthesis of connective tissue components by fibroblasts through the secretion of transforming growth factor-beta₁ (TGF-β₁) [47,48]. In patients with CVI, a pathologically high level of TGF-β₁ is detected, which increases in proportion to the severity of the disease. TGF-β₁ binds to dermal fibroblasts and extracellular matrix proteins, promoting fibroblast proliferation and triggering the development of fibrosis.

An important fact is the decrease in the proliferative response of fibroblasts to TGF-$\beta₁ $ stimulation as the severity of the disease increases. In patients with venous trophic ulcers, fibroblasts acquire morphological characteristics typical of senescent cells. The hyporesponsiveness of venous ulcer fibroblasts is associated with a 4-fold decrease in the number of type II TGF-$\beta₁ $ receptors. This leads to impaired phosphorylation of SMAD proteins (types 2 and 3) and p42/44 mitogen-activated protein kinases, as well as a reduction in collagen and fibronectin synthesis by venous ulcer fibroblasts compared to cells from intact skin [49]. The growth rate of venous ulcer fibroblasts is significantly reduced, including upon stimulation with basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and interleukin-1 (IL-1) [50].

Proliferating fibroblasts actively synthesize matrix metalloproteinases (MMPs), which begin to predominate over tissue inhibitors of metalloproteinases (TIMPs) [6, 27, 28]. MMP synthesis is also triggered by the activation of proteases in the extracellular matrix, the secretion of cytokines and growth factors, and the disruption of intercellular contacts. Their exact role in the pathological process remains not fully understood. There are reports of increased levels of MMP-1, MMP-2, and TIMP-1 in the skin during lipodermatosclerosis. Directly around the trophic ulcer, several studies have detected MMP-9, while in unhealed venous trophic ulcers themselves, MMP-1 and MMP-8 were found. Concurrently, a decrease in the level of the TIMP-1 inhibitor was noted. One of the functions of MMPs in CVD is the degradation of the extracellular matrix, the formation of venous ulcers, and the inhibition of their healing.

Chronic venous insufficiency (CVI) proceeds with a cascade of inflammatory reactions in the soft tissues of the lower extremities. At the first stage, lipodermatosclerosis develops, in which, against the background of preserved soft tissue structure, an increase in the capillary bed area occurs—not due to an increase in their absolute number, but as a result of their elongation and tortuosity. Microscopic examination reveals infiltration of the papillary dermis by monocytes, macrophages, connective tissue proteins, and fibrin, which concentrates around capillaries in the form of a "cuff." Small numbers of T-lymphocytes are also detected. At this stage, vascular endothelial growth factor (VEGF-A) begins to be produced [51, 52]. It stimulates the expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin by endothelial cells, which mediate leukocyte binding to the endothelium and facilitate their penetration into the tissue [51]. In addition to inducing the synthesis of cell adhesion molecules, VEGF-A is a potent mitogen for endothelial cells, increases vascular permeability, and regulates the expression of MMPs and TIMPs [53]. Plasma VEGF concentrations in blood from the lower extremities in patients with CVD classes 3–4 are significantly higher than in healthy individuals [54].

Changes at the macrocirculatory level characteristic of CVD are mediated either by venous obstruction caused by impaired venous outflow or by the incompetence of venous valves causing reflux [55]. The manifestation of this is dynamic venous "hypertension," which essentially represents the inability to sufficiently reduce venous pressure as a result of muscle pump activation [56]. Direct pressure measurements in the dorsal foot vein, as well as plethysmography results, demonstrate that after active calf muscle contractions upon relaxation, venous pressure remains higher than in healthy individuals, and the time required for venous pressure to return to baseline values is significantly shortened [55, 56].

1.3 Epidemiology of the Disease or Condition

In the 1970s, the first epidemiological studies were conducted, which mainly assessed the prevalence of varicose veins. It was shown that among the adult population of various countries, the frequency of the disease ranges from 2% to 60% [57, 58], which is primarily associated with ethnic differences. In African countries and the Pacific region, the incidence of varicose veins rarely exceeds 5–6%, whereas in Europe this figure reaches tens of percent among the entire adult population.

Risk factors for the development of CVD are traditionally recognized as age, female sex, obesity, and heredity. Specific female risk factors include pregnancy, use of hormonal medications (estrogens, progestogens), and menopause [58–62]. At the same time, not all conducted studies confirm a significant dependence of CVD risk on sex [57, 63]. The role of pregnancy and childbirth in the genesis of varicose veins is evidenced by the data of numerous works [57, 60, 64]. Excess body weight is considered one of the potential risk factors for CVD. However, evaluating this factor in isolation is quite difficult, since in most cases a high body mass index is associated with a higher frequency of pregnancies and childbirth in the obstetric history of women [60, 65–68]. Heredity is, quite reasonably, recognized as a risk factor for CVD [60, 69, 70].

One of the largest-scale epidemiological studies conducted using the CEAP classification to describe cases of CVD was the Vein Consult program, which included 91,545 individuals from 20 countries worldwide [57]. CVD was found in 83.6% of the study participants. Among patients with CVD, women (68.4%) predominated over men (31.6%). The average age of the examined individuals with CVD was 53.3 years, and the distribution by disease class was as follows: C0S – 19.7%, C1 – 21.7%, C2 – 17.9%, C3 – 14.7%, C4 – 7.5%, C5 – 1.4%, C6 – 0.7%.

A recent meta-analysis combining data from 19 epidemiological studies demonstrates the following prevalence of CVD by clinical class: C0s – 9%, C1 – 26%, C2 – 19%, C3 – 8%, C4 – 4%, C5 – 1%, C6 – 0.42% [71]. Meanwhile, the main risk factors for the development of CVD and chronic lower limb varicose veins are female sex, age, overweight and obesity, prolonged standing posture, family history, number of pregnancies, and Caucasian ethnicity. Regarding the number of pregnancies, most studies confirm an increase in the risk of chronic lower limb varicose veins by 1.1 times for each pregnancy up to 2.3 times in the presence of 4 or more pregnancies [57, 60, 64]. However, these figures may be skewed by the age and ethnicity of the women. As for hormonal medication use, smoking, and social status, no reliable impact of these factors on the risk of developing CVD and chronic lower limb varicose veins has been identified [71].

In the Russian Federation, the frequency of chronic venous disease (CVD) has been studied in several trials [72–74]. Only one of them, which had a cross-sectional design, evaluated the prevalence of venous pathology in the general population. In 2015, during an examination of residents in a rural settlement in the Central Federal District of Russia, symptoms of CVD were identified in 69.3% of 703 individuals aged over 18 years [60]. The distribution by clinical classes was as follows: C0s – 4.7%, C1 – 34.3%, C2 – 21.3%, C3 – 4.5%, C4 – 2.6%, C5 – 1.0%, C6 – 0.1%. Among nosological variants, telangiectasias and reticular veins were found in 34.1% of residents, varicose veins in 29.0%, and post-thrombotic syndrome was diagnosed in 1.4% of cases. Chronic venous insufficiency (CVI) was diagnosed in 8.2%. The analysis of risk factors for the development of CVD and varicose veins showed that heredity, age, female sex, number of pregnancies, and menopause are significant for the development of CVD. For varicose veins, the risk factors were age, heredity, and menopause.

The high prevalence of CVD in our country emphasizes the importance of accurate and timely diagnosis of this pathology, as well as the need for treatment technologies that can be applied as widely as possible—not only by cardiovascular specialists and phlebologists, but also by general surgeons and even physicians of other specialties.

1.4 Features of Coding the Disease or Condition

International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes:

Varicose veins of lower extremities (I83):

I83.0 Varicose veins of lower extremities with ulcer

Any condition classifiable in rubric I83.9 with ulcer or specified as ulcerated

Varicose ulcer (lower extremity, any part)

I83.1 Varicose veins of lower extremities with inflammation

Any condition classifiable in rubric I83.9 with inflammation or specified as inflamed

I83.2 Varicose veins of lower extremities with ulcer and inflammation

Any condition classifiable in rubric I83.9 with ulcer and inflammation

I83.9 Varicose veins of lower extremities without ulcer or inflammation

Phlebectasia of lower extremity (any part) or unspecified site

Varicose veins of lower extremity (any part) or unspecified site

Varicose veins of lower extremities (any part) or unspecified site

1.5 Classification of the disease or condition

The classification of CVD must meet the demands of both daily practice and research work in phlebology. These requirements are satisfied by the CEAP classification, which takes into account clinical manifestations (C – clinic), etiology (E – etiology), anatomical localization (A – anatomy), and pathogenesis (P – pathogenesis) of the disease. The CEAP classification is recommended for use by all leading professional phlebological associations [75–80]. Active use of the CEAP classification in the work of healthcare institutions is advisable.

The CEAP classification is presented in Table 1.

Table 1. CEAP classification of chronic venous disorders

Basic and expanded classification options. When describing a patient's phlebological status, either basic or expanded classification options can be used. For medical institutions and physicians specializing in the treatment of chronic venous disease (CVD), the expanded option is preferred. The basic option is the one in which the clinical class is indicated based on the most pronounced clinical sign, while the pathophysiological section notes only the mere presence of reflux, occlusion, or their absence. In the expanded option, the clinical class designation is used with the enumeration of all available objective and subjective manifestations and the indication of those segments of the venous system in which pathological changes (reflux or occlusion) were detected. Each hemodynamically significant section of the lower extremity venous bed is assigned a letter designation (Table 2).

Table 2. Designations of venous system segments

A patient's status described using the presented terms is not static. Dynamics can be either positive (successful treatment) or negative (disease progression), therefore it is essential to record the date of diagnosis. The abbreviations En, An, Pn typically denote cases of typical venous stasis symptoms (edema, pain, heaviness, fatigue, nocturnal cramps, pruritus, burning) in patients with a completely normal venous system under the influence of certain factors (physical overstrain, prolonged orthostasis, hormonal therapy, etc.). In other words, these refer to so-called phlebopathies. Given the update of the CEAP classification in 2020, it is advisable to use abbreviated letter designations for venous system segments (instead of numerical ones) when formulating the diagnosis [80].

Example of a diagnosis formulation according to the CEAP classification

The female patient consulted a phlebologist on September 3, 2020. She complains of varicose veins in the left lower extremity, edema of the distal leg, and pain and heaviness in the calf muscles in the afternoon. Duplex scanning of the lower extremity veins was performed: deep veins – unremarkable, valve incompetence of the great saphenous vein in the thigh, incompetence of the perforating vein in the middle third of the thigh.

Diagnosis formulation according to the CEAP classification:

Basic option: C3s, Ep, As, p, Pr; 03.09.2020; LII.

Full option: C2,3s, Ep, As, p, Pr (GSVa, TPV); 03.09.2020; LII.

In domestic phlebology, a nosological approach to diagnosis formulation is adopted. Varicose veins (Ep) involving superficial vein transformation, post-thrombotic disease (Es) affecting the deep venous system, and congenital developmental anomalies of the venous system – phlebodysplasias (Ec) are distinguished. The use of nosological formulations in clinical practice allows the physician to quickly navigate the patient's medical records, so it is advisable to use these terms simultaneously with the CEAP classification. The case described above can be characterized as follows: Varicose veins of the left lower extremity. C2,3s, Ep, As, p, Pr (GSVa, TPV); 03.09.2020; LII.

1.6 Clinical presentation of the disease or condition

The clinical presentation in uncomplicated varicose veins (clinical class C2 according to the CEAP classification) is determined by the presence of palpable and standing-visible nodular and/or tortuous subcutaneous veins with a diameter of more than 3 mm. The presence of varicose veins may be accompanied by subjective symptoms (pain or discomfort in the area of varicose veins, sensation of pulsation, sensation of tightness (compression), heaviness, rapid fatigability, sensation of edema, cramps, skin pruritus, "restless" legs, tingling sensation, sensation of warmth or burning). In complicated forms of varicose veins (chronic venous insufficiency – clinical classes C3–C6 according to the CEAP classification), in addition to varicose veins, the following may appear: lower leg edema, changes in skin color and structure – hyperpigmentation, atrophie blanche, venous eczema (predominantly in the projection of varicose veins), trophic ulcers.

2. Diagnostics, medical indications and contraindications for diagnostic methods

General provisions on diagnosis

LNC 5 LeC C

Comment. Clinical examination includes analysis of patient complaints, anamnesis taking, and physical examination (inspection and palpation).

LNC 5 LeC C

Comment. As a result of inspection, evaluation of complaints, anamnestic data, and palpation, the nosological variant of CVD and treatment strategy can be determined in the majority of patients: the patient should undergo surgery or only conservative treatment is necessary. If invasive treatment is not going to be used, omitting further examination is not an error. However, if secondary varicose veins are suspected due to probable pathology of the deep venous system or pelvic veins, scheduling a routine planned examination is recommended.

LNC 5 LeC C

Criteria for establishing the diagnosis (condition)

The criterion for establishing the diagnosis of lower extremity varicose veins is the presence of palpable and standing-visible nodular and/or tortuous subcutaneous veins with a diameter of more than 3 mm.

In patients with well-developed subcutaneous adipose tissue, if there are doubts during inspection, an ultrasound examination should be performed. Non-tortuous visible subcutaneous veins lacking nodular local dilations, which sometimes contour in people with thin skin and sparse adipose tissue, should be considered normal.

2.1 Complaints and Anamnesis

- Pain: aching, dull

- Sensation of pulsation, pulsating pain

- Sensation of tightness, compression

- Heaviness

- Rapid leg fatigue

- Sensation of edema

- Cramps

- Skin pruritus

- "Restless" legs (restless legs syndrome)

- Tingling sensation

- Sensation of warmth or burning

LNC 5 LeC C

Comment. The indicated symptoms are not pathognomonic. For a number of these symptoms, sensitivity, specificity, and likelihood ratio (LR – likelihood ratio, the probability that a symptom will be detected in a patient with the disease relative to the probability that it will be detected in a healthy person) have been studied. It should be borne in mind that these data were obtained in a study with significant methodological limitations and not for all presented symptoms [83]. Summary data on the sensitivity and specificity of venous symptoms are presented in Table 3

Table 3. Summary data on the sensitivity and specificity of venous symptoms [83]

- Symptoms worsen with insufficient activity of the calf muscle-venous pump (prolonged static standing or sitting) or towards the end of the day;

- Symptoms regress after walking, resting in a horizontal position, or using medical compression hosiery;

- Seasonal variation in the intensity of venous insufficiency manifestations is possible;

- In young and middle-aged women, complaints may increase during or before menstruation.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. The described complaints are widespread in the population and occur regardless of the presence or absence of CVD [84]. The prevalence of symptoms tends to increase with age, regardless of gender. The correlation between the severity of these symptoms and the clinical manifestations of venous disease is low and has no direct diagnostic value [82,85]. It should also be borne in mind that sometimes lower limb pain during walking with preserved peripheral arterial pulsation (venous intermittent claudication) may be caused by high-level venous outflow obstruction (inferior vena cava or iliac veins) due to prior thrombosis or May-Thurner syndrome [86,87]. History taking allows for differential diagnosis between primary, secondary, or congenital superficial varicose veins. Patients must be questioned about a history of thrombophlebitis and deep vein thrombosis. A gynecological and medication history (including hormonal drugs, allergies, etc.) must also be collected, taking into account possible comorbid conditions, including heart and kidney diseases, which may also influence the course of CVD [81].

2.2 Physical Examination

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Objective signs of CVD are:

- telangiectasias (TEL);

- reticular veins (RV);

- varicose veins (transformation) of subcutaneous veins;

- edema;

- trophic disorders.

These manifestations can be found in various combinations. Identifying TEL, RV, and varicose transformation of subcutaneous veins generally does not cause difficulties.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Lower limb edema, changes in skin color and structure, including ulcerations, can be caused by various reasons, and therefore their presence requires a thorough differential diagnosis.

LNC 5 LeC C

Commentary. Varicose transformation of veins in the indicated areas may be a sign of obstruction of the iliac veins, inferior vena cava (IVC), gonadal vein incompetence, nutcracker syndrome (compression of the left renal vein between the superior mesenteric artery and the aorta) or retroaortic course, and a sign of renal cell carcinoma.

LNC 5 LeC C

Commentary. If a weak pulse wave is detected, further examination is recommended

LE 2 GSR A

Commentary. Traditional clinical tests, including tourniquet tests such as Trendelenburg, Perthes, and others, are nowadays of historical interest only and should not be used in diagnosis and treatment planning.

2.3 Laboratory Diagnostics

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Additional laboratory or instrumental methods for diagnosing concomitant pathology can be prescribed at the discretion of the attending physician, depending on the nature of the planned treatment and anesthetic management.

2.4 Instrumental Diagnostics

2.4.1. Duplex scanning of lower extremity veins (A04.12.006.002)

Ultrasound examination of the veins with a formalized report should be performed by a specialist in ultrasound diagnostics. To clarify the features of the venous system lesion and determine the treatment strategy, ultrasound examination of the veins may be performed by a physician who does not hold a certificate in ultrasound diagnostics, with the results entered into the consultation report text. Independent vein scanning by the clinician significantly improves the quality of medical care provided. For better perception, it is advisable to graphically display the duplex ultrasound results.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Duplex scanning is largely an "operator-dependent" method. Its quality is influenced not only by the experience and knowledge of the examiner, but also by the tactical approaches to the treatment of venous diseases adopted in the given medical institution. The results of ultrasound scanning play an auxiliary role in the vast majority of cases. Treatment strategy is determined primarily based on clinical examination data.

• Duplex scanning is recommended as the first-line instrumental method when planning invasive treatment for patients with lower extremity varicose veins [75,76,78,89,90].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Duplex scanning is a method of venous ultrasound examination in which, if necessary, two or three scanning modes can be used simultaneously. The main mode is B-mode, and additional modes may include color flow mapping, pulsed-wave Doppler, or a combination thereof. This combination allows simultaneous visualization of the vessel under study, determination of blood flow direction and parameters. The method provides information on the anatomy and hemodynamics of the venous bed, including valvular incompetence and venous obstruction [91–95]. Duplex scanning is the "gold standard" of instrumental examination for patients with lower extremity varicose veins. This method is non-invasive and has high reproducibility. Lower extremity ultrasound examination to confirm the diagnosis and refine the treatment strategy can be performed by any specialist engaged in the diagnosis and treatment of venous diseases who has practical experience in performing ultrasound examinations

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• During duplex scanning, it is recommended to evaluate the anatomy (location features) of the veins, compressibility, and characteristics of venous blood flow, including reflux duration [75,76,78].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. The technique of venous duplex scanning has been developed and described in detail by many authors [96–103]. Ultrasound devices equipped with linear transducers operating at a frequency of 5–13 MHz are used. In everyday practice, the capabilities of inexpensive portable devices are sufficient. For scanning deep veins, especially in obese patients, as well as when examining pelvic and retroperitoneal veins, convex transducers with a lower emission frequency (3.5–5 MHz) are used. Settings optimized for low-flow evaluation (5–10 cm/s) should be used for visualization [89].

LE 3 GSR C

Commentary. Examination of blood reflux in the supine position can yield both false-positive and false-negative results [98]. If necessary (the patient cannot stand for the time required for the examination), veins below the mid-thigh can be localized in the sitting position with the leg semi-flexed and relaxed. Examination in the supine position is performed to assess the deep venous system of the lower extremities, pelvic cavity, and retroperitoneal space. When examining in the supine position to assess reflux, the head of the examination table should be elevated to an angle of 45°.

• To assess the competence of the saphenofemoral junction (SFJ), the proximal segment of the great saphenous vein (GSV), and the common femoral vein (CFV), the Valsalva maneuver and distal compression tests in the standing position of the patient are recommended [75,76,78].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Reflux is evaluated during the Valsalva maneuver (breath-holding with straining to increase intra-abdominal pressure) and distal compression tests (both manual and using a pneumatic cuff). The Valsalva maneuver is used to assess the state of the saphenofemoral junction and the proximal segment of the common femoral vein.

• Venous segments located distally to the proximal segment of the GSV and CFV are recommended to be evaluated using distal compression tests [75,76,78].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. To simulate walking, the patient transfers weight from the limb under study to the other, maintaining support on the heel, and performs dorsiflexion of the foot with a fixed heel.

LE 3 GSR C

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. The described changes should expediently be interpreted as "functional" and the clinical and ultrasound picture should be evaluated dynamically. The presence of reflux lasting more than 0.5 seconds in the absence of varicose veins is not an absolute basis for prescribing invasive treatment.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. The hemodynamic significance of perforating veins should be evaluated only taking into account the clinical presentation and the anatomical variant of varicose veins of the lower extremities. Currently, criteria for perforating vein incompetence are not precisely defined. Research data are contradictory. Reflux durations of 0.35 and 0.5 seconds have been proposed, with a diameter of at least 3.5 mm [89,104]. However, none of the ultrasound parameters (diameter, duration of reflux, bidirectional blood flow) can be the basis for recognizing a particular perforating vein as incompetent. Even incompetent perforating veins (according to ultrasound scanning data) continue to perform their natural drainage function during physical exertion. The hemodynamic significance of a perforating vein is assessed by the clinician taking into account the clinical presentation. It must be remembered that intervention on perforating veins is carried out selectively, especially in the presence of pathological reflux in the main superficial veins and their tributaries, the elimination of which can significantly reduce the duration of reflux through the perforator. One can unambiguously speak of the hemodynamic significance of an incompetent perforating vein only if it is the direct and sole entry point of reflux into varicose superficial veins.

- the source of reflux via the incompetent GSV, small saphenous vein (SSV), or anterior accessory great saphenous vein (AAGSV) (junction with deep veins, perforating vein, perineal veins, etc.);

- diameters of the incompetent GSV in the upright position at the level of the SFJ; in the middle third of the thigh; in the upper third of the calf, in the middle third of the calf;

- extent of reflux along the GSV in the upright position (from … to …);

- structural variant of the incompetent GSV;

- diameters of the incompetent SSV in the upright position at the level of the saphenopopliteal junction (SPJ), in the upper and middle thirds of the calf;

- extent of reflux along the SSV in the upright position (from … to …);

- presence, localization, and diameter in the upright position of incompetent perforating veins of the thigh and calf having a connection with varicose superficial veins.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. In patients for whom some form of surgical intervention is planned, it is advisable to reflect in the report the presence of individual anatomical features (true duplications, local dilatations, significant tortuosity of main veins, reflux along the main vein with a competent ostial valve, etc.). Measurement and recording of vein diameters may be regulated by the protocol of the medical institution .

2.4.2. Additional instrumental diagnostic methods.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

• Ultrasound duplex scanning (A04.12.002.002 Ultrasound Doppler examination of lower extremity veins) is not recommended as an independent diagnostic method in patients with CVD [75,76,78].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Doppler ultrasound provides acoustic information that allows one to judge the presence or absence of blood flow. Based on changes in sound signals during functional tests, a conclusion can be made about the direction of blood flow, i.e., detecting blood reflux. At the same time, Doppler ultrasound does not provide any information about the anatomy of the venous bed, which makes it impossible to recommend it as an independent study method in patients scheduled for surgical intervention [105,106].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

2.5 Other Procedures

• To assess the severity of CVD, it is recommended to use the VCSS scale [75,76,78].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. The CVD severity rating scale is known in world literature as VCSS (Venous Clinical Severity Score) [107,108]. The scale uses a number of clinical signs, which are assigned a score equivalent depending on their severity (Appendix G1, "VCSS – CVD Severity Score Scale"). The sum of scores reflects the severity of the pathology – the higher the score, the more severe the course of CVD. Changes in the sum of scores over time make it possible to assess the degree of disease progression or the effectiveness of therapeutic measures.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Commentary. Currently, for Russian-speaking patients, the vein-specific quality of life questionnaire CIVIQ (Appendix G3. CIVIQ Questionnaire for assessing the quality of life of a patient with chronic venous disease) and the general quality of life questionnaire SF36 (Appendix G4. SF36 Questionnaire for assessing the quality of life of a patient with chronic disease) have been validated [109,110]. Assessing quality of life using the SF36 questionnaire requires the application of a special calculation methodology; simple score tallying is not permissible.

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

3.1. Compression treatment

Elastic compression of the lower extremities (compression therapy) plays a key role in the conservative treatment of venous diseases. It can be used independently or in addition to invasive interventions.

Goals of compression therapy:

• Reduction in severity or elimination of subjective symptoms of CVD;

• Prevention of development and reduction in severity of edema;

• Reduction of manifestations of lipodermatosclerosis;

• Acceleration of healing and prevention of recurrence of trophic ulcers;

• Reduction of pain levels and shortening of rehabilitation periods after invasive treatment for varicose veins;

• Improvement of quality of life through the reduction in severity or elimination of subjective symptoms of CVD and objective manifestations of chronic venous insufficiency (CVI).

Contraindications to compression therapy [111]:

• Severe forms of chronic lower limb ischemia (CLLI) with ABI <0.6, or ankle pressure <60 mm Hg, or toe pressure <30 mm Hg, or transcutaneous oxygen tension <20 mm Hg.

• Suspected compression of subcutaneous arterial shunts

• Severe heart failure (NYHA IV)

• Heart failure NYHA III in the absence of objective indications and clinical-hemodynamic monitoring

• Confirmed allergy to the material

Before prescribing compression in patients with chronic venous disease (CVD) of any class, the risk-benefit ratio must always be evaluated, taking into account the potential negative impact on arterial blood flow and allergies to compression garment components. It should be noted that despite physicians' prescriptions, many elderly patients do not use compression knitwear, and in a significant number of cases, outside assistance is required to put them on [112, 113]. Donning devices significantly improve the ability of elderly CVD patients to successfully use compression stockings [114].

Level of Evidence 2, Grade of Recommendation B

Comment. To date, there is a lack of comparative studies on various types of compression garments and their application regimens. Further study of this issue is required for evidence-based recommendations [118].

• Elastic compression is recommended for patients with C2–C6 CVD to relieve subjective symptoms [115–117].

Level of Evidence 2, Grade of Recommendation B

Comment. Despite a limited number of large randomized controlled trials, a large body of non-randomized studies has now accumulated, indicating a reduction in the severity of venous symptoms and an improvement in the quality of life in CVD patients using compression treatment [119–123], while the magnitude of compression at the ankle level should be from 10 to 30 mm Hg.

LE 2 GSR A

Comment. The use of medical elastic compression garments (MECG), even of low pressure (10–20 mm Hg), can reduce CVD symptoms and edema. The pressure level should be adapted to the severity of the disease and limited to the lowest pressure that provides relief from symptoms and edema. This will also improve patient compliance. In the presence of massive edema, it is advisable to start treatment with bandages for edema reduction, followed by a transition to compression knitwear.

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. For patients with trophic disorders, the optimal approach is the use of class 2 or 3 knitwear or bandages made of short-stretch (non-stretch) bandages. Randomized clinical trials on the use of compression knitwear for skin trophic changes in CVD have not been conducted; the recommendation is based on experimental data demonstrating improved microcirculation and tissue oxygenation during compression therapy.

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. The use of below-knee MECGs reduces the area of lipodermatosclerosis in patients with healed venous ulcers. In patients who used compression below-knee stockings, the area of lipodermatosclerosis significantly decreased compared to the control group after 6 and 12 months

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. A systematic review showed that the use of elastic compression compared to its absence is associated with a 54% reduction in the risk of trophic ulcer recurrence (RR, 0.46; 95% CI, 0.27–0.76). At the same time, a significant advantage of class 3 compression over class 2 was found only at a follow-up period of up to 3 years, but not up to 5 years.

• To eliminate or reduce symptoms of CVD or manifestations of chronic venous insufficiency (CVI), it is recommended to use compression garments in CVD patients awaiting surgery or in patients for whom surgical intervention is not planned [115, 116].

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. A systematic literature review showed that today there is no convincing evidence of delayed progression of lower extremity varicose veins as a result of compression therapy [115]. Meanwhile, one low-quality RCT demonstrated a reduction in the recurrence rate of varicose veins 1 year after phlebectomy from 71% to 6% with the use of compression knitwear [134]. Thus, further studies are required to clarify this issue.

• Elastic compression for at least one week is recommended after open surgical treatment of varicose veins to reduce the risk of postoperative complications [115, 116, 135].

LRE 1, GR A

Comment. A meta-analysis including the results of 4 RCTs showed that compression therapy after open surgical treatment of varicose veins reduces postoperative pain syndrome, the number of complications, and accelerates return to work. At the same time, the results of compression for one week were comparable to a longer duration of its application (3–6 weeks) [136, 137]. The results of a later RCT confirmed that the use of compression knitwear for 7 days after phlebectomy compared to the use of a compression bandage for 24 hours is associated with a significant reduction in postoperative pain intensity [135]. Both elastic stockings and bandages can improve the results of surgical treatment [138, 139].

Level of Evidence 2, Grade of Recommendation B

Comment. Literature data indicate that the use of compression knitwear with a pressure of 35 mm Hg after endovenous laser ablation (EVLA) for one week helped reduce pain syndrome and improve the quality of life of operated patients compared to two-day compression [140]. The use of compression knitwear with a pressure of 23–32 mm Hg after radiofrequency ablation (RFA) for 4 hours reduced the number of complications and the volume of the operated limb [141]. At the same time, the results of these studies should be interpreted with caution. The necessity, duration, and degree of compression after endovenous thermal interventions require further study and currently can be determined by the physician's preferences. In the absence of postoperative pain, CVD symptoms, and CVI manifestations, the use of elastic compression is not a necessary measure.

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. According to various studies, there is a positive effect of compression therapy after sclerotherapy in terms of reducing pigmentation and improving the cosmetic effect [115, 116]. Nevertheless, the question regarding the duration and degree of compression therapy remains open. Thus, there was no difference in efficacy, number of phlebitis cases, skin discoloration, quality of life, or level of pain syndrome when comparing the use of compression for 24 hours and 5 days [144]. A systematic review showed that the use of compression knitwear with a pressure of 35 mm Hg compared to 23 mm Hg after foam sclerotherapy of trunks and miniphlebectomy is associated with a reduction in the severity of main symptoms (pain, burning, sensory disturbance, heaviness). Initial data from the CONFETTI RCT confirm the benefit of using class 2 compression knitwear for 7 days after foam sclerotherapy of varicose tributaries regarding pain severity, but not other side effects and complications [145, 146]. Further randomized controlled trials are needed to establish the role of compression after foam sclerotherapy of large veins. To date, indications for its use and the compression regimen cannot be standardized.

Level of Evidence 2, Grade of Recommendation B

Comment. A prospective randomized study did not reveal a reduction in the risk of lower extremity varicose veins in pregnant women wearing compression knitwear with a pressure of 18–32 mm Hg [148]. At the same time, a statistically significant reduction in the incidence of pathological reflux in the great saphenous veins was noted, along with an improvement in venous symptoms. Further research on the use of elastic compression in pregnant women is needed.

LRE 1, GR A

3.2. Pharmacotherapy

3.2.1. General provisions

Systematic reviews and clinical studies on the pharmacotherapy of chronic venous disease (CVD) have examined a wide range of medicinal products, some of which are not registered in the Russian Federation (RF). These guidelines cover only drugs that are registered in the RF and listed in the State Register of Medicines (SRM) [150].

Pharmacotherapy for CVD utilizes medications belonging to various ATC groups. What unites these drugs is proven efficacy in achieving the goals of pharmacotherapy (see section 3.2.1.2 "Goals of Pharmacotherapy for CVD"). Table 4 shows the correspondence between the nonproprietary names of drugs (drug groups) used for CVD therapy in scientific publications and their international nonproprietary names (INNs) and Anatomical Therapeutic Chemical (ATC) classification groups. For convenience, these drugs are generally referred to hereinafter as phlebotropic drugs (PTDs).

Table 4. Correspondence of drug names (drug groups) used in scientific publications to international nonproprietary names and groups according to the Anatomical Therapeutic Chemical (ATC) classification.

^aATC – Anatomical Therapeutic Chemical classification

^bProducts with the INN "Hesperidin + Diosmin" included in the ATC group "C05CA53 Diosmin, combinations" may include products with both micronized and non-micronized diosmin.

- Reduction in severity or elimination of subjective symptoms of CVD;

- Prevention of development and reduction in severity of venous edema;

- Reduction in manifestations of lipodermatosclerosis;

- Acceleration of trophic ulcer healing;

- Prevention and treatment of adverse (side) effects after invasive treatment for varicose veins;

- Improvement of quality of life by reducing the severity or eliminating subjective symptoms of CVD and objective manifestations of chronic venous insufficiency (CVI).

• Oral phlebotropic drugs are recommended as safe agents for relieving CVD symptoms [151].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. Available data allow for the assessment of the safety of vasoactive drugs only in the short-term follow-up period. Safety in the medium- and long-term follow-up periods cannot be evaluated based on the available data [151]. Moderate-quality evidence indicates that the phlebotropic group increases the risk of mild adverse effects compared to placebo (RR 1.21, 95% CI 1.05–1.41). The most frequent side effects are gastrointestinal disorders [151]. Adverse events are more frequently associated with the intake of rutosides (ATC: rutoside, combinations) and calcium dobesilate. Some side effects may be omitted from data analysis in systematic reviews due to the short follow-up period and small number of patients in the included studies. In particular, in one case-control study, the relative risk of agranulocytosis associated with calcium dobesilate intake was 39.55 (95% CI, 17.96–77.49) with an incidence of 1.21 cases per 10,000 patient-years [152]. In another study, the RR of agranulocytosis with calcium dobesilate intake was 77.84 (95% CI, 4.50–1346.2) [153]. In a systematic review with meta-analysis of sulodexide use in CVD, the risk of adverse events (AEs) did not differ between sulodexide and placebo (RR 1.31, 95% CI 0.74–2.32; 270 participants). The overall risk of AEs with sulodexide intake was low: 3% (95% CI 1–4%) as estimated by 3,656 participants.

3.2.2. Efficacy of oral venoactive drugs regarding CVD symptoms

The efficacy of one drug demonstrated in an RCT should not be extrapolated to other drugs of the same or similar composition, since formal registration documents obtained by manufacturers of generic or similar agents are not based on clinical efficacy data for these drugs. In the absence of RCT results for the efficacy of a particular drug, the results of studies with a lower level of evidence should be analyzed carefully, adhering to the same principle of the inadmissible nature of extrapolation.

• For the pharmacological reduction of venous symptoms in patients with CVD, it is recommended to use the following medications: hesperidin+diosmin, diosmin, calcium dobesilate, MPFF, rutosides (ATC: C05CA51, Rutoside, combinations), horse chestnut seed extract (INN: Aesculus hippocastanum seed extract), Ruscus extract (Ruscus + HMC + AA) (INN: Ascorbic acid + Hesperidin methylchalcone + Ruscus aculeatus rhizome extract) [151, 154, 155].

LRE 1, GR A

Comment 1. According to a Cochrane systematic review from 2020, PTDs have limited activity against certain venous symptoms and venous edema [151]. In this review, the efficacy of PTDs was assessed against only 7 symptoms (pain, cramps, restless legs syndrome, itching, heaviness, feeling of swelling, paresthesia (tingling sensation, burning sensation)); diosmin-containing drugs (hesperidin+diosmin, diosmin, MPFF) were not separated by composition and structural forms and were described within the diosmin-containing drug group. The data of this review regarding the efficacy of diosmin-containing drugs (including MPFF) in relation to paresthesias and heat/burning sensation (efficacy not established) do not agree with the data of an earlier systematic review of RCTs regarding the efficacy of MPFF for the specified symptoms (efficacy established) [156].

Comment 2. Purified micronized flavonoid fraction (diosmin + flavonoids expressed as hesperidin) (MPFF). According to a 2018 systematic review of double-blind placebo-controlled RCTs, as well as a 2017 systematic review on the use of MPFF in patients with CVD, the efficacy of this drug has been demonstrated regarding: leg pain, heaviness, feeling of swelling, cramps, paresthesias, heat/burning sensation, and functional discomfort [156, 157]. A prospective international multicenter single-arm study RELIEF demonstrated the efficacy of MPFF regarding pain, feeling of swelling, cramps, as well as in improving quality of life according to the vein-specific CIVIQ questionnaire [158].

Comment 3. A Cochrane systematic review with meta-analysis demonstrated the efficacy of horse chestnut seed extract regarding venous pain and itching [154].

Comment 4. Ruscus extract (Ruscus + HMC + AA). In most clinical studies and systematic reviews, Ruscus extract refers to a three-component drug consisting of *Ruscus aculeatus* rhizome extract (ruscus), hesperidin methylchalcone, and ascorbic acid. Systematic reviews of RCTs have proven the efficacy of this drug regarding pain, cramps, heaviness, sensation of swelling, fatigue, paresthesias, and pruritus. [155, 159]

Comment 5. The efficacy of a number of VADs was evaluated in a 2022 umbrella review of systematic reviews [160]. An analysis of reviews including MPFF, Ruscus + HMC + AA, hydroxyethylrutosides (ATC: C05CA51, Rutoside, combinations), diosmin, horse chestnut seed extract, and sulodexide was performed. The efficacy of several VADs regarding certain CVI symptoms was confirmed: pain (MPFF, horse chestnut seed extract, Ruscus extract), heaviness (MPFF, Ruscus extract, hydroxyethylrutosides) (ATC: C05CA51, Rutoside, combinations), sensation of swelling (MPFF, Ruscus extract), paresthesias (MPFF, Ruscus extract), cramps (MPFF, hydroxyethylrutosides (ATC: C05CA51, Rutoside, combinations)), burning sensation (MPFF), and pruritus (horse chestnut seed extract).

• For the pharmacological reduction of venous symptoms in patients with CVI, the use of sulodexide is recommended [161].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. The efficacy of sulodexide regarding venous symptoms is summarized in a systematic review with meta-analysis of comparative and non-comparative studies [161]. Sulodexide has been shown to be effective in reducing pain, cramps, feeling of heaviness, and edema. The prospective, multicenter, non-comparative observational ALLEGRO study demonstrated the efficacy of sulodexide regarding 11 venous symptoms in patients with C3–C4 CVI [162–164].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. In the presence of CVI, the use of VADs may be aimed not at symptom relief, but at manifestations of CVI (venous edema, lipodermatosclerosis, venous ulcer).

• During the hot season, for patients with subjective CVI symptoms, it is recommended to consider monotherapy with hesperidin + diosmin preparations, without prescribing compression therapy [165].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

• For the pharmacological reduction of venous edema in patients with CVI, the use of preparations based on diosmin, rutosides (ATC: rutoside, combinations), and Ruscus extract (Ruscus + HMC + AA) is recommended [151, 155].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment 1. The efficacy of VADs regarding venous edema was investigated in a 2020 Cochrane review according to three parameters: edema (dichotomous variable), ankle circumference, and calf volume [151]. Consistent data across all three parameters were obtained only for diosmin-based preparations. Data for calcium dobesilate and rutosides (ATC: rutoside, combinations) are contradictory. The efficacy of red vine leaf extract (dietary supplement) was not evaluated in this review.

Comment 2. The efficacy regarding venous edema of MPFF, diosmin, and rutosides (ATC: rutoside, combinations) was demonstrated in a 2012 systematic review with meta-analysis [166]. For MPFF, additional data on venous edema efficacy were obtained in the prospective, international, multicenter, non-comparative RELIEF study (evaluated by ankle circumference) [158]. The efficacy of horse chestnut seed extract regarding edema was shown in a 2012 Cochrane systematic review with meta-analysis (evaluated by reduction in calf volume, calf circumference, and ankle circumference) [154]. The efficacy of Ruscus extract (Ruscus + HMC + AA) regarding edema has been shown in two systematic reviews of RCTs [155, 159].

Comment 3. A 2022 umbrella review of systematic reviews demonstrated the efficacy of MPFF, Ruscus extract, horse chestnut seed extract, and hydroxyethylrutosides (ATC: C05CA51, Rutoside, combinations) regarding edema [160].

• For the pharmacological reduction of venous edema in patients with CVI, the use of sulodexide is recommended [161].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. The efficacy of sulodexide regarding edema was demonstrated in a 2020 systematic review with meta-analysis [161], as well as in the prospective, multicenter, non-comparative observational ALLEGRO study [162–164].

3.2.2.3. Acceleration of venous trophic ulcer healing and reduction of trophic disorders severity

• For the pharmacological acceleration of venous trophic ulcer healing in patients with CVI, it is recommended to use MPFF (INN: purified micronized flavonoid fraction [diosmin + flavonoids expressed as hesperidin]) or #sulodexide orally (250 or 500 LSU twice daily) as an adjunct to compression therapy [167, 168].

LRE 1, GR A

Comment. A 2016 Cochrane systematic review, based on a meta-analysis of data from 4 RCTs, demonstrated an increased rate of venous ulcer healing when #sulodexide was added to local therapy (RR 1.66; 95% CI 1.30–2.12) [168]. According to a meta-analysis of 5 RCTs, the use of MPFF for 6 months in addition to standard therapy increases the chance of venous trophic ulcer healing by 32% (95% CI, 3%–70%) and significantly reduces the mean healing time from 21 to 16 weeks [167]. According to a network meta-analysis, adjuvant therapy with #sulodexide demonstrated the highest probability of being the best treatment ensuring complete ulcer healing compared to MPFF and pentoxifylline. https://pubmed.ncbi.nlm.nih.gov/33983078/ A 2020 Cochrane review analyzed publications on the efficacy of calcium dobesilate, diosmin, and rutosides in the treatment of venous ulcers. No confirmation of the efficacy of these drugs was obtained. Studies on #sulodexide were not included in this review. Guidelines from foreign professional societies have for several years suggested using MPFF and #sulodexide in the treatment of long-standing or large venous ulcers as an adjunct to compression therapy [78, 169].

A 2022 umbrella review of systematic reviews demonstrated the efficacy of MPFF and #sulodexide in accelerating venous ulcer healing. Conflicting information was obtained regarding the efficacy of hydroxyethylrutosides (ATC: C05CA51, Rutoside, combinations) [160].

• For the pharmacological reduction of trophic disorders severity in patients with CVI, it is recommended to use preparations based on diosmin (INN: Hesperidin + Diosmin and Purified micronized flavonoid fraction [diosmin + flavonoids expressed as hesperidin]) [151].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. The efficacy of diosmin-containing preparations regarding the severity of trophic disorders was shown in a 2020 Cochrane review, with the quality of evidence assessed as "moderate" [151]. These data are supported by an additional sensitivity analysis excluding studies using compression. Also, a previously performed meta-analysis of 7 RCTs demonstrated a significant reduction in skin hyperemia (RR, 0.50; 95% CI, 0.27–0.94) and trophic changes (RR, 0.18; 95% CI, 0.07–0.46) with MPFF use [156].

• For the pharmacological reduction of trophic disorders severity in patients with CVI, the use of sulodexide is recommended [161].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. A systematic review with meta-analysis on the effect of sulodexide on certain CVI symptoms and manifestations proves its efficacy regarding skin discoloration in the area of trophic disorders [161]. The prospective, multicenter, non-comparative observational ALLEGRO study demonstrated the efficacy of sulodexide regarding objective manifestations of CVI (edema, induration, hyperpigmentation) [162–164].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. The studies included in the systematic review pertained to various interventions ("open" varicose vein surgery [ligation and stripping], endovenous thermal ablation [EVLA and RFA], sclerotherapy), had significant design differences, and were conducted without blinding. Four out of five studies demonstrated efficacy according to the specified parameters, while one study showed no efficacy. MPFF was used in all studies, and sulodexide was additionally used in one study. The results of these studies require confirmation in larger, more methodologically sound RCTs.

Level of Evidence 2, Grade of Recommendation C

Comment. A single RCT demonstrated a decrease in the incidence, area, and intensity of hyperpigmentation 1 month after sclerotherapy of telangiectasias and reticular veins with #sulodexide. Meanwhile, at 3 months of follow-up, there were no significant differences despite ongoing therapy [171]. The feasibility of using VADs to reduce hyperpigmentation during cosmetic sclerotherapy of small-caliber veins largely depends on the patient's preferred timeline for initiating and performing sclerotherapy and the cost of periprocedural pharmacotherapy. The use of VADs does not affect the final outcome of cosmetic sclerotherapy for small-caliber veins.

3.2.3. Use of venoactive drugs in pregnant and lactating women

• The use of VADs during pregnancy to alleviate vein-specific symptoms is recommended only if the pregnant woman is informed about the lack of high-quality evidence regarding the efficacy and safety of these drugs, and when non-pharmacological methods for relieving venous symptoms are ineffective [171].

LNC 4 LeC C

Comment 1. The efficacy of various interventions for relieving vein-specific symptoms and edema associated with varicose veins in pregnant women was evaluated in a 2015 Cochrane systematic review. According to the authors, based on a single study, moderate-quality evidence was obtained regarding the efficacy of rutosides (ATC: C05CA51, Rutoside, combinations) for chronic venous disease (CVD) symptoms [147]. It should be noted that in systematic reviews, the safety of VADs can only be assessed over short follow-up periods and in small patient groups. The highest-quality data on the safety of VAD use during pregnancy to date are presented in a retrospective study by Lacroix I. et al. [172]. This study covered a wide range of drugs, with hesperidin and diosmin preparations accounting for the largest share. The study group comprised 8,998 pregnant women prescribed VADs, including 1,200 cases of VAD prescription during the period of organogenesis, and the control group comprised 27,963 pregnant women without VAD prescriptions. No adverse effects of venoactive drugs during pregnancy were identified.

Comment 2. Manufacturers' instructions for various VADs do not recommend their use during pregnancy, restrict it, or permit it with the wording that the expected benefit to the mother and potential risk to the fetus must be weighed. However, such an assessment is impossible due to the lack of quality information on fetal risks and the symptomatic focus of the therapy. Before prescribing a specific drug, its applicability during pregnancy should be checked in the current product monograph available in the State Register of Medicines [150].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

3.2.4. Regimen and dosing of venoactive drugs

LNC 5 LeC C

Comment. Exceeding standard daily doses does not always enhance the clinical effect, but it increases the frequency of adverse drug reactions. At the same time, a number of studies indicate that in certain clinical situations, increasing the dose of a phlebotropic drug may enhance its therapeutic efficacy. The dose and dosing regimen of a venoactive drug may be modified after documentary justification and obtaining informed consent from the patient.

LE 4 GSR C

It is advisable to prescribe phlebotropic drugs as monotherapy, as there is no evidence of an enhanced therapeutic effect when two or more drugs are taken simultaneously, while their combined use increases the likelihood of adverse reactions.

3.2.5. Topical dosage forms in the treatment of CVD

• Topical dosage forms (ATC: C05BA53 Heparin, combinations) are recommended for use in patients with CVD for the rapid relief of vein-specific symptoms [173–178].

LNC 4 LeC C

Comment. To date, there are no high-quality placebo-controlled RCTs on the use of topical VAD formulations. The authors of the 2020 Cochrane systematic review on the efficacy and safety of VADs found no studies with topical agents meeting the inclusion criteria for the analysis [151].

Among all topical agents, the most studied is a combination drug based on heparin, escin, and essential phospholipids (ATC: C05BA53 Heparin, combinations), which demonstrates significant improvement in skin microcirculation in patients with CVD [173–175]. In observational studies, its use either alone or in combination with systemic VADs and compression therapy was associated with a significant decrease in the intensity of vein-specific symptoms (heaviness, fatigue, pain, cramps, sensation of swelling), a reduction in calf volume, and an improvement in quality of life [177,178]. It should be noted that the therapeutic effect of topical drugs may be related to the evaporation of volatile components (local hypothermia) and massage during application and rubbing of the product.

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. Certain studies demonstrate that the use of topical agents based on escin, heparin, and essential phospholipids after sclerotherapy and percutaneous laser coagulation of telangiectasias and reticular veins promotes faster disappearance of vascular elements and reduces the incidence of ecchymoses, phlebitis, hyperpigmentation, and neovascularization.

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. To date, the purpose of topical VAD use is the relief of vein-specific symptoms. Therefore, in the absence of such symptoms, the use of topical dosage forms containing VADs is not recommended.

3.3. Phlebosclerosing treatment

The objective of sclerotherapy is significant damage to the endothelium and subendothelial structures, which leads to the formation of a specific blood clot in the vein lumen, cessation of blood flow through it, and subsequent transformation of the vein into a fibrous cord. The goal of sclerotherapy is not to achieve vein thrombosis, which can recanalize, but rather fibrosis (sclerosis) of the vein. In this case, the result of sclerotherapy is equivalent to surgical treatment.

3.3.1. Indications for sclerotherapy

• Sclerotherapy is recommended to eliminate varicose veins in patients with CVD [183].

LE 2 GSR A

Comment. When compared with placebo, intravenous injections of C05BB02 Polidocanol effectively eliminate varicose veins in the lower extremities [183]. Meanwhile, in patients without truncal reflux, when eliminating varicose syndrome, some studies demonstrate advantages of sclerotherapy over open surgery regarding clinical outcomes [184], while others show a higher recurrence rate in the long-term follow-up period after sclerotherapy [185].

• Sclerotherapy is recommended to eliminate incompetent perforating veins acting as a source of reflux in patients with CVD [186–189].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. According to a systematic review with meta-analysis of 35 studies, sclerotherapy for incompetent perforating veins provides a short-term technical success rate (30 days) of 58% (95% CI, 48–68%) after a single session and 70% (53–84%) after repeated injections, while the long-term occlusion rate (12 months) reaches 83% (95% CI, 74–90%) without an increased risk of complications [188]. According to another systematic review with meta-analysis, the rate of successful venous leg ulcer healing after sclerotherapy reaches 99.9% (95% CI, 81–100%) with a follow-up of up to 1 year [189].

• Sclerotherapy is recommended to eliminate residual varicose veins after prior intervention in patients with chronic venous disease (CVD) [190,191].

Level of Evidence 2, Grade of Recommendation B

• Sclerotherapy is recommended to eliminate recurrent varicose veins after prior intervention in patients with CVD [192–194].

LNC 4 LeC C

• Sclerotherapy is recommended to treat varicose veins with reflux originating from pelvic veins in patients with CVD [195,196].

LNC 4 LeC C

Comment. In the presence of varicose veins caused by pelvic venous reflux, sclerotherapy can be performed either alone or in combination with the elimination of reflux in the ovarian veins and the great saphenous vein (GSV) system [195,196].

• Sclerotherapy is recommended for patients with venous leg ulcers when open and endovenous methods are impossible, inappropriate, or contraindicated (including patients with severe comorbid conditions), as well as to accelerate ulcer healing during preparation for surgical intervention [188,189,194,197–199].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

3.3.2. Contraindications to sclerotherapy

LNC 5 LeC C

Comment. Sclerotherapy is not recommended within 12 weeks of deep vein thrombosis (DVT) or pulmonary embolism (PE), within 6 weeks of superficial vein thrombosis (SVT) with a moderate or high risk of extension into the deep venous system, or within 2 weeks of SVT with a low risk of extension into the deep venous system. Severe neurological complications include transient ischemic attack, acute cerebrovascular accident (stroke), and epileptic seizure. Other neurological complications include transient visual disturbances (floaters, accommodation disorders, visual field defects, scotomas), speech disorders, and migraine with or without aura. Severe cardiovascular complications may manifest as acute coronary syndrome, life-threatening arrhythmias, etc. Critical ischemia is defined by characteristic clinical manifestations (rest pain, trophic tissue defects) as well as an ankle-brachial index (ABI) <0.5 and/or systolic arterial pressure in the tibial arteries <50 mm Hg in patients with known lower extremity peripheral artery disease [200,201].

LNC 5 LeC C

Comment. A systematic review identified 21 cases of stroke or TIA associated with sclerotherapy. Of these, only 11 patients had a confirmed intracardiac right-to-left shunt, predominantly in the form of a patent foramen ovale. It was also noted that in 5 out of 13 cases of confirmed stroke, there were no signs of thrombotic or air occlusion of the cerebral arteries [202]. In an experimental study involving 20 patients with suspected respiratory or neurological symptoms after foam sclerotherapy, the detection of air bubbles in the left heart chambers and cerebral vessels did not affect the incidence of adverse events [203]. Thus, a proven right-to-left shunt is not a mandatory prerequisite for complications. The literature discusses mechanisms of complications such as cerebral and coronary vasospasm mediated by endothelin-1 released from endothelium damaged during sclerotherapy [204]. Therefore, current guidelines and consensus statements do not support routine screening of patients for asymptomatic right-to-left shunts prior to sclerotherapy [200,201]. Moreover, in patients with a confirmed asymptomatic patent foramen ovale, the feasibility of sclerotherapy is considered provided that techniques minimizing the risk of air and thrombotic cerebral embolism are strictly followed (routine pharmacoprophylaxis, use of liquid sclerotherapy or foam based on a physiological gas mixture of CO₂/O₂).

LNC 5 LeC C

Comment. In these situations, sclerotherapy may be used if an individual risk-benefit assessment has been performed and the expected individual benefit significantly outweighs the individual risk.

3.3.3. Sclerotherapy methods

• To perform sclerotherapy, it is recommended to use venosclerosing drugs (lauromacrogol 400 (ATC: C05BB02 Polidocanol), sodium tetradecyl sulfate (ATC: C05BB04)) in patients with CVD [205].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. Sodium tetradecyl sulfate (ATC: C05BB04) and lauromacrogol 400 (ATC: C05BB02 Polidocanol), both in liquid and foam forms, have similar efficacy and tolerability. No differences were noted between the two drugs regarding vessel clearance or adverse events [205]. Certain studies have shown a lower incidence of skin reactions (including necrosis) with C05BB02 Polidocanol compared to sodium tetradecyl sulfate when treating small-caliber veins [206,207].

• Venosclerosing drugs for sclerotherapy are recommended to be used as a liquid or foam in patients with CVD [205].

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. Meta-analyses show no statistically significant differences between liquid and foam sclerotherapy for varicose veins [205]; however, individual studies indicate advantages of foam over liquid lauromacrogol 400 (ATC: C05BB02 Polidocanol) in the sclerotherapy of varicose tributaries [208], the GSV trunk [209–211], as well as telangiectasias and reticular veins in obese patients [212].

• Following sclerotherapy, the use of medical compression stockings or a compression bandage is recommended [138,143,144,213].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

LNC 5 LeC C

Comment. Concentrations and volumes recommended by the manufacturer are indicative and may be adjusted based on the clinical situation and the clinician's experience [200].

Level of Evidence 2, Grade of Recommendation B

Comment. For clearly visible and palpable varicose veins, administration of the sclerosing agent is permissible without ultrasound guidance [200,215].

• The foam form of venosclerosing drugs is recommended to be prepared using the Tessari method (using two syringes connected via a three-way stopcock by mixing the liquid sclerosing agent and ambient air in a 1:4 or 1:5 ratio, or a mixture of oxygen and carbon dioxide in the same ratios) for sclerotherapy in patients with CVD [216].

LNC 4 LeC C

Comment. The use of non-sterile atmospheric air does not pose a risk of bacterial contamination of the foamed form of vein-sclerosing agents, which determines the lack of need for sterile air mixtures [217, 218]. Some studies have shown that the administration of large volumes of foam (more than 10 ml) prepared with a mixture of carbon dioxide and oxygen is associated with a lower number of complications [219, 220], while other works have not demonstrated a reduction in the frequency of neurological disorders when using smaller volumes of foam (up to 10 ml) [221, 222].

• Administration of the foamed form of vein-sclerosing drugs is recommended to be carried out within the shortest possible time from the moment of its preparation during sclerotherapy in patients with CVD [200].

LNC 5 LeC C

• During a single session, it is recommended to administer no more than 10 ml of the foamed form of the vein-sclerosing drug [200].

LNC 5 LeC C

Comment. To date, there is no objective evidence to establish the maximum permissible and safe volume of the foamed form of a vein-sclerosing drug for a single administration. At the same time, there are data linking the volume of injected foam with the incidence of serious neurological disorders [223]. Thus, a volume of 10 ml has been accepted by international and Russian experts as the maximum amount of the foamed form of a sclerosant that ensures safe administration in a single session.

3.3.4. Adverse reactions and complications of sclerotherapy

• To avoid skin necrosis, it is recommended to avoid administering large volumes of vein-sclerosing drugs under excessive pressure during sclerotherapy in patients with CVD [200].

LNC 5 LeC C

• To reduce the risk of persistent hyperpigmentation, it is recommended to use compression hosiery during sclerotherapy in patients with CVD [224–226].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

• To reduce the risk of persistent hyperpigmentation, it is recommended to consider the possibility of removing blood clots from the vein lumen [224–226].

Level of Evidence C (UDD 2), Grade of Recommendation A (UUR A)

Comment. It is hypothesized that the removal of blood clots from the sclerosed vein by aspiration through a thick needle or by expression through micro-punctures within 1 to 3 weeks helps reduce the severity of hyperpigmentation after sclerotherapy. At the same time, only one study has investigated this issue, and no differences were demonstrated, although clot removal led to faster resolution of pain and inflammation, but only for vessels with a diameter of 1–3 mm [224].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. The expediency of using FVAs to reduce the severity of hyperpigmentation during sclerotherapy of small-caliber veins for cosmetic purposes largely depends on the patient's preferred timelines for initiating and performing sclerobliteration, and the cost of the periprocedural course of drug therapy. The use of FVAs does not affect the final outcome of small-caliber vein sclerobliteration performed for cosmetic purposes.

LNC 5 LeC C

Comment. Up to 30% of the general population has a patent foramen ovale, which allows air bubbles to enter the cerebral arterial system [202]. This figure significantly exceeds the incidence of neurological disorders during foam sclerotherapy. Moreover, to date, only the relationship between patent foramen ovale and ischemic stroke has been convincingly proven, but not other neurological reactions; furthermore, there is a lack of direct correlation between the detection of foam in the left heart chambers and cerebral vessels and the frequency of neurological symptoms [203]. Thus, total screening of all patients before sclerotherapy is considered inappropriate.

• In patients with a history of neurological complications during previously performed sclerotherapy, it is recommended to perform sclerotherapy only if the individual benefit significantly outweighs the risk, to prefer the liquid form of the drug, to avoid administering large volumes of the vein-sclerosing agent, and to avoid activation and straining immediately after the injection [200, 201].

LNC 5 LeC C

LNC 5 LeC C

• In patients with a high individual risk of VTE (history of VTE episodes, positive family history of VTE, verified hereditary thrombophilia), it is recommended to perform sclerotherapy only if the individual benefit significantly outweighs the risk, to carry out pharmacoprophylaxis in accordance with current guidelines, to use elastic compression, to avoid large drug volumes, and to ensure early ambulation after injection [200, 201].

LNC 5 LeC C

3.4. Surgical treatment

3.4.1. Goals of surgical treatment, indications for surgical treatment of varicose veins

Goals of surgical treatment in patients with lower extremity varicose veins:

• Elimination of the cosmetic defect caused by varicose veins;

• Reduction or elimination of subjective symptoms of CVD;

• Prevention of progressive varicose transformation of superficial veins;

• Prevention of bleeding from varicose veins;

• Prevention of varicotrombophlebitis;

• Prevention of development and reduction of severity of venous edema;

• Prevention of development and progression of chronic venous insufficiency (venous edema, hyperpigmentation, lipodermatosclerosis);

• Reduction of manifestations of lipodermatosclerosis;

• Accelerating healing and preventing recurrence of venous trophic ulcers;

• Improving quality of life by eliminating or reducing the cosmetic defect caused by varicose veins, reducing or eliminating subjective symptoms of CVD and objective manifestations of CVI.

The tasks of surgical treatment are:

• elimination of pathological vertical and/or horizontal reflux;

• elimination of varicose-transformed superficial veins.

Intervention for varicose veins may include elimination of pathological vertical or horizontal reflux and elimination of varicose veins. None of the listed elements is mandatory (for example, isolated removal of varicose veins is possible, or conversely, isolated thermal ablation of main superficial veins without intervention on tributaries). Various technologies can be used to solve similar technical tasks (for example, to eliminate pathological reflux in the GSV, its removal, thermal ablation, sclerobliteration, or non-thermal non-tumescent [NTNT] ablation can be used).

Surgical intervention in most cases combines several methods performed simultaneously or in stages. The use of various combinations of methods must be justified by the characteristics and severity of pathological changes in the venous system.

• In patients with lower extremity varicose veins (CVD C2–C6), surgical treatment is recommended to eliminate the cosmetic defect caused by varicose veins; reduce or eliminate subjective symptoms of CVD; prevent progressive varicose transformation of superficial veins; prevent bleeding from varicose veins; prevent varicotrombophlebitis; prevent development and reduce severity of venous edema; prevent development and progression of chronic venous insufficiency (venous edema, hyperpigmentation, lipodermatosclerosis); reduce manifestations of lipodermatosclerosis; accelerate healing and prevent recurrence of venous trophic ulcers; improve quality of life by eliminating or reducing the cosmetic defect caused by varicose veins, reducing or eliminating subjective symptoms of CVD and objective manifestations of CVI [227–229].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. Surgical treatment showed better results regarding the regression of chronic venous disease (CVD) symptoms, cosmetic effect, patient satisfaction, and quality of life in patients with uncomplicated varicose veins compared to conservative treatment [227–229]. From a pharmacoeconomic perspective, all types of surgical treatment for varicose veins demonstrate advantages over conservative therapy in terms of quality-adjusted life years (QALY), with EVLA having the lowest cost per quality-adjusted life year [230]. It should be noted that the advantage of surgical intervention over conservative therapy has been evaluated primarily for early forms of CVD (C2), whereas its effect on venous edema and trophic disorders may be less pronounced [78,231].

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. As part of a pilot observational comparative study, no differences were found in the dynamics of changes in disease severity and quality of life over 6 months of follow-up in symptomatic patients with C1s CVD and GSV trunk reflux after thermal ablation or elastic compression therapy [232]. In rare cases, reflux in the specified veins may be considered clinically significant and serve as an indication for surgical intervention in the absence of varicose changes in tributaries (e.g., the appearance of other signs of CVD in the incompetent vein basin: telangiectasias and/or reticular veins).

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment. Performing the intervention on both limbs simultaneously does not increase the risk of complications and does not significantly enhance postoperative discomfort

3.4.2. VTE prophylaxis in venous surgery

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. A systematic review of publications on thermal ablation indicated that there were no reports of fatal complications, and the incidence of severe VTE did not exceed 1% [239]. According to a large retrospective study, the incidence of VTE after combined phlebectomy and endovenous treatment methods is 0.15–0.35% in the first 30 days, 0.26–0.50% within 90 days, and 0.46–0.58% within one year. The incidence of symptomatic VTE after sclerotherapy is lower than after open surgery or thermal ablation in the first 30 days; no significant differences between methods in the incidence of VTE at other time points were found [240]. Meanwhile, the incidence of subclinical thrombotic complications, predominantly manifested as calf muscle vein involvement, can reach 18–19% in open interventions [241–243] and 20–23% after sclerotherapy. According to the analysis of the MAUDE (Manufacturer and User Facility Device Experience) database—a voluntarily updated database of device-related complications—the incidence of DVT after thermal ablation is 1 case per 2,500 interventions, PE is 1 per 10,000, death from VTE is 1 per 50,000, and 7 cases of fatal perioperative PE have been registered [244]. The incidence of VTE after combined phlebectomy reaches 5.3% [245]. It should be considered that VTE can develop in a delayed manner; cases of PE have been described 3 weeks after EVLA [239].

• To assess the risk of VTE after surgical treatment, it is recommended to use the Caprini scale [78,236,237,246].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. The Caprini scale is available in Appendix G (Table G4 "Caprini risk assessment model for venous thromboembolism in surgical patients undergoing modern minimally invasive procedures on superficial veins"). It should be noted that the Caprini scale is not validated for patients receiving treatment for varicose veins. Such validation is necessary because existing literature data on the incidence of VTE after invasive treatment for lower extremity varicose veins are extremely heterogeneous. According to several sources, VTE after endovenous laser ablation (EVLA) is relatively common (2–5%) [239, 247–249]. According to the Manufacturer and User Facility Device Experience (MAUDE) database analysis from 2000 to 2012, an increase in VTE accompanied the expansion of thermal ablation techniques, with the peak VTE rate recorded in 2008, after which it stabilized [244]. According to this study, over the past 5 years, the incidence of VTE following EVLA and radiofrequency ablation (RFA) has been 1 and 2 per 10,000 procedures, respectively. VTE structure: DVT <1:2500, PE <1:10000, mortality <1:50000. Available data do not allow for the reliable identification of patient groups in whom VTE pharmacoprophylaxis is unquestionably indicated, nor do they determine the optimal duration, intensity of anticoagulation, optimal drug, or establish a correlation between the need for anticoagulation and the type of intervention [250–252]. Initial results from the validation of the Caprini scale following modern minimally invasive procedures on superficial veins demonstrated a significant correlation between scores and the incidence of asymptomatic postoperative thromboses, predominantly in the form of distal vein thrombotic occlusion and heat-induced thermal injury (endovenous heat-induced thrombosis). Based on the analysis, routine pharmacoprophylaxis was shown to be unnecessary for preventing symptomatic VTE, the incidence of which did not exceed 0.5%. Taking into account both symptomatic and asymptomatic VTE, it was proposed to divide patients into low-risk (0–6 points: VTE rate without pharmacoprophylaxis — 2.6%), moderate-risk (7–10 points: VTE rate without pharmacoprophylaxis — 8.5%), and high-risk groups (11 points or more: VTE rate without pharmacoprophylaxis — 33.3%).

• All patients after surgical treatment are recommended to receive VTE prophylaxis measures in accordance with their individually assessed risk [253–256].

LoE 2 GoR C

Comment. Modern minimally invasive surgical methods for varicose veins are characterized by the default use of non-specific VTE prophylaxis methods, such as early mobilization and elastic compression. The main issue is the appropriateness of using prophylactic doses of anticoagulants (ATC: B01, antithrombotic agents). Systematic reviews and meta-analyses published in recent years do not demonstrate clear and reliable benefits of pharmacological prophylaxis when performing modern interventions on varicose veins due to the low incidence of VTE, especially symptomatic forms. Therefore, routine pharmacological prophylaxis does not appear justified. Taking into account the interim results of the CAPSIVS study, the use of prophylactic doses of anticoagulants (ATC: B01, antithrombotic agents) may be considered in patients with a moderate risk of VTE (7-10 Caprini scores), especially in the presence of additional risk factors related to the procedure (removal of varicose tributaries, perforator vein intervention, simultaneous intervention on >1 vein, surgery duration >45 min, non-ambulatory setting, non-tumescent anesthesia) and a high risk of VTE (11 or more Caprini scores), as well as in individuals with a history of DVT, superficial thrombophlebitis, or PE [257–259]. The duration of pharmacoprophylaxis should be at least 7 days for the moderate-risk group, 7–30 days for the high-risk group, and 30 days or longer for individuals with a history of VTE. It should be noted that a single dose of an anticoagulant (ATC: B01, antithrombotic agents) on the day of surgery is not an effective method for preventing complications. Available parenteral anticoagulants (ATC: B01, antithrombotic agents) (UFH, LMWH (B01AB Heparin group), and #fondaparinux sodium) in doses recommended by the manufacturer for the respective risk groups can be used as pharmacological agents. In recent years, accumulating data have confirmed the efficacy and safety of DOACs (ATC: B01A Antithrombotic agents), specifically #rivaroxaban** 10 mg for VTE prophylaxis [238]. Pharmacoprophylaxis regimens are presented in Appendix A3.2 («Recommended methods of VTE prophylaxis depending on individually assessed risk»). The regimens for using #rivaroxaban** and #fondaparinux sodium in perioperative VTE prophylaxis trials for varicose vein surgery differ from standard recommendations for the general surgical population.

LNC 5 LeC C

3.4.3. Elimination of vertical reflux

• To eliminate pathological vertical reflux, thermal ablation methods are recommended as preferred over open surgery [176, 230, 260–264].

LE 1 GR B

Comment 1. In general, thermal ablation methods appear more preferable for eliminating pathological vertical reflux compared to open surgery [75, 76, 78, 169, 264, 265] and compared to non-thermal non-tumescent (NTNT) methods [169]. Numerous systematic reviews and RCT meta-analyses demonstrate that thermal ablation of superficial veins is comparable in efficacy to open surgery in the short- and long-term perspective, but is associated with a significantly lower incidence of complications, mainly due to a reduced risk of wound infection, hematomas, and paresthesias [261]. From a pharmacoeconomic perspective, EVLA and RFA proved to be the most effective interventions compared to NTNT and conservative treatment [230].

Comment 2. Open surgery is justified if EVLA or RFA cannot be performed due to organizational, financial, or other reasons. Open surgery is not inferior to endovenous interventions in the immediate, medium-, and long-term periods. The invasiveness of open surgery can be reduced through the use of small incisions and invagination stripping. Such interventions can be performed on an outpatient basis under tumescent anesthesia. The results of such interventions regarding the risk of hematomas and hemorrhages, pain levels, and patient quality of life in the early postoperative period are comparable to endovenous saphenous vein ablation methods [199, 266].

• To eliminate pathological vertical reflux, thermal ablation methods are recommended as preferred over scleroablation and NTNT methods [176, 230, 261–264].

Level of Evidence 1, Grade of Recommendation B

Comment. A Cochrane review of publications on thermal ablation, open surgery, and sclerotherapy for great saphena vein (GSV) disease indicates that EVLA, RFA, and sclerotherapy are at least no less effective than stripping [265]. Systematic reviews have demonstrated lower efficacy for sclerotherapy methods, while data comparing thermal ablation and open surgery are contradictory [267, 268]. A Cochrane review of publications on the use of thermal ablation, open surgery, and sclerotherapy for small saphenous vein (SSV) disease demonstrates greater efficacy of EVLA compared to phlebectomy and sclerotherapy [264]. The issue of eliminating reflux in the SSV has been additionally studied in a systematic review with data meta-analysis [269]. Despite the lack of convincing evidence in individual RCTs, guidelines from various authoritative professional associations recognize thermal ablation methods as preferred for eliminating pathological vertical reflux compared to sclerotherapy [78, 169, 176]. Numerous modern systematic reviews with meta-analyses of RCT results state that thermal methods have increased efficacy compared to sclerotherapy, both in terms of technical outcomes and long-term varicose vein recurrence [261, 262]. From a pharmacoeconomic analysis perspective, despite its low cost, sclerotherapy is significantly inferior to open surgery as well as to thermal and non-thermal non-tumescent (NTNT) ablation methods [230]. NTNT methods avoid the negative effects of tumescent anesthesia and thermal tissue damage (pain, allergic reactions to the anesthetic, damage to paravascular tissues), rare cases of technical problems associated with instrument damage, and the formation of heat-induced thrombosis, while maintaining high short-term efficacy. High efficacy of NTNT methods compared to thermal methods is noted in terms of reduced pain and bruising [270]. Comparative evaluation of the efficacy and safety of NTNT remains difficult due to the limited number of RCTs and the lack of long-term results in comparative studies [169, 269, 271–275].

UDD 5 URC C

Comment. The optimal approach for GSV high ligation is along the inguinal crease. The GSV must be ligated flush with the femoral vein. There is no need to suture the saphenous opening (fossa ovalis) or subcutaneous tissue after high ligation.

LE 2 GSR A

• During open surgery, it is recommended to perform both high ligation and stripping of the GSV rather than high ligation alone in patients with lower limb varicose veins [278, 279].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. Previous studies have shown that the combination of high ligation and removal (stripping) of the great saphenous vein trunk significantly reduced the risk of reintervention compared to patients who underwent high ligation alone [278, 279], while there was no difference in the visual progression of varicose veins.

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. In the vast majority of cases (80–90%), GSV reflux is registered from the junction only down to the upper third of the leg. Removal of the GSV along its entire length is accompanied by a significantly higher incidence of superficial nerve injury [280], while the recurrence rate of varicose veins does not decrease. The remaining vein segment can later be used for reconstructive vascular surgery. If it is necessary to eliminate GSV reflux on the leg, short stripping can be combined with sclerotherapy of the leg segment of the GSV.

UDD 2 URC B

Comment. Invagination methods (including PIN-stripping) or cryostripping are less traumatic than standard Babcock vein removal [281–286].

UDD 4 URC C

Comment. Surgical interventions on the SSV should be performed with the patient in the prone position. The anatomy of the terminal segment of the SSV is highly variable, therefore ligation and removal should not be performed without a preliminary ultrasound examination of the SPJ zone. The exact location of the junction and the pattern of reflux propagation should be clarified using preoperative ultrasound scanning.

UDD 5 URC C

Comment. There is no convincing evidence that ligating the SSV immediately adjacent to the SPJ is superior to ligating it 3–5 cm away from the popliteal vein, close to the skin [81]. Ligation of the SSV 3–5 cm away from the SPJ helps reduce incision size and lowers the risk of complications associated with deep dissection.

UDD 5 URC C

Comment. Ligation of the saphenopopliteal junction of the SSV is recommended to be performed via a transverse approach in the popliteal fossa. The vein should be removed only within the limits where reflux is detected. Reflux in the lower third of the leg is rare; furthermore, removing the vein in this area increases the risk of damaging the sural nerve, which runs in close proximity to the SSV.

UDD 5 URC C

Comment. Indications for deep venous valve correction are currently under study. In a significant number of cases with varicose vein disease, effective elimination of pathological reflux in superficial veins leads to regression of reflux in deep veins. Moreover, most studies on deep vein reflux correction in primary varicose veins are based on the treatment of patients with chronic venous insufficiency (CEAP classes C3–C6) [76].

UDD 5 URC C

Comment. Surgical intervention on deep veins is indicated only for patients with classes C5–C6 and grade 3–4 deep vein reflux (down to the knee joint level and below) according to the Kistner classification, as well as in cases of failure of all previously used surgical and conservative treatment methods. There is evidence that correction of hemodynamic disorders in deep veins improves the results of surgical treatment for lower limb varicose veins. Thus, in one study with a median follow-up of 6.2 years, the recurrence rate after phlebectomy was 17.3%, while after phlebectomy combined with valvuloplasty, it was 7.7% [289]. Furthermore, limbs with corrected deep vein valve function did not experience ulcer recurrence, among other things. Deep vein valve correction surgery cannot be recommended for routine practice and should be performed in specialized centers with substantial experience in deep venous surgery. In cases of coexisting lower limb varicose veins and non-thrombotic iliac vein obstruction, existing studies show conflicting results, indicating both the benefits of combined correction of reflux and obstruction and good outcomes from isolated interventions. Given the lower invasiveness, complexity, and cost of superficial reflux correction, it is advisable to begin treatment with such procedures [290].

UDD 1 URC B

Comment 1. The data presented below concern high ligation (crossectomy) and stripping of the great saphenous vein (GSV) or small saphenous vein (SSV) and do not apply to miniphlebectomy. A review of 17 RCTs (2,624 interventions) found that combined phlebectomy is more frequently associated with wound complications, whereas thermal ablation is more commonly associated with phlebitis [260]. Removal of superficial veins (both truncal and their tributaries) can lead to nerve damage with the development of transient or persistent paresthesia. Data regarding the impact of GSV stripping direction on the risk of nerve injury are contradictory [280, 291, 293]. GSV removal restricted to the knee level reduces the risk of nerve damage, though it does not eliminate it entirely; the incidence of this complication with short stripping remains at 7%–10% [280, 293]. At the same time, leaving the calf segment of the GSV in place, as shown in a large long-term longitudinal study, causes varicose vein recurrence in 4% of cases [279]. The incidence of common peroneal nerve injury during crossectomy and SSV stripping reaches 5%–7%, and sural nerve injury reaches 2%–4% [294, 295]. The risk of femoral vein or artery injury is extremely low (0.0017%–0.3%), but this complication is extremely dangerous because it is not always recognized in a timely manner [292]. A systematic review of 87 studies identified 87 cases of major vessel injury. Removal of the femoral or popliteal vein was described in five cases, and femoral artery removal in 17 cases [292].

Comment 2. In a large retrospective study covering more than 260,000 invasive procedures, the incidence of VTE following "open surgery" and endovenous techniques is 0.15%–0.35% at 30 days, 0.26%–0.50% at 90 days, and 0.46%–0.58% at 1 year, with no statistically significant differences between the methods [240]. However, the incidence of VTE following combined phlebectomy reaches 5.3% and even 18.3% [241].

• To reduce the risk of infectious complications, antibiotic prophylaxis is recommended in patients with chronic venous disease undergoing open surgical treatment [252, 253, 296, 297].

LE 2 GR A

Comment. The incidence of surgical site infection in open operations ranges from 1.5% to 16% [296]. According to RCT data, the use of antibiotic prophylaxis in open surgeries reduces the incidence of wound infection complications by almost half [297]. Accordingly, antibiotic prophylaxis is recommended during open surgery (except for isolated miniphlebectomies or those supplementing endovenous interventions). In doing so, guidance should be taken from the Federal Clinical Guidelines "Principles of Organizing Perioperative Antibiotic Prophylaxis in Healthcare Facilities" [298]. Aside from wound infection, lymphorrhea is a fairly frequent complication of open surgeries, with an incidence reaching 1.3% [293].

• To relieve postoperative pain, the administration of NSAIDs (non-steroidal anti-inflammatory and antirheumatic drugs (ATC M01A)) per os is recommended [76, 78].

Level of Reliability of Evidence 5, Level of Recommendation C

Level of Reliability of Evidence 5, Level of Recommendation C

Level of Reliability of Evidence 5, Level of Recommendation C

In clinical practice, to designate medical services regarding endovenous thermal methods of action on the venous wall, the terms coagulation, obliteration, and ablation may be considered synonymous. Thus, in accordance with the Order of the Russian Ministry of Health No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services," thermal obliteration methods include the following designations: "laser coagulation of lower extremity veins," "endovenous laser coagulation of lower extremity veins," and "radiofrequency coagulation of lower extremity veins."

Thermal vein obliteration methods are based on endovenous thermal injury to the venous wall, leading to occlusive fibrosis and transformation of the vein into a connective tissue cord—i.e., the disappearance of the vein as a morphological and functioning structure [299–302].

• Endovenous laser and radiofrequency obliteration (radiofrequency thermal ablation) are recommended for the elimination of truncal reflux in the GSV [78, 169, 176, 230, 261–265].

LRE 1, GR A

Comment. Performed meta-analyses demonstrate that thermal ablation methods are not inferior to open surgery regarding the incidence of clinical disease recurrence in the short and long term (follow-up up to 5 years), but are characterized by a lower risk of neoangiogenesis and technical failures, lower levels of postoperative pain, and a shorter rehabilitation period.

• Endovenous laser and radiofrequency obliteration (radiofrequency thermal ablation) are recommended for the elimination of truncal reflux in the SSV [264, 303].

Evidence level 1, grade of recommendation C

Comment. To date, a small number of comparative studies have been conducted to evaluate the efficacy and safety of thermal obliteration of the SSV trunk. Available data indicate high technical efficacy of EVLA and RFA, including advantages over open surgery. Meanwhile, the optimal treatment modality has not yet been determined.

• Endovenous laser and radiofrequency obliteration (radiofrequency thermal ablation) are recommended for the elimination of reflux in the intersaphenous vein (Giacomini vein) [304, 305].

LE 4 GSR C

• Endovenous laser and radiofrequency obliteration (radiofrequency thermal ablation) are recommended for the elimination of reflux in the anterior accessory great saphenous vein [306].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. According to a systematic review, thermal ablation of the anterior accessory great saphenous vein is associated with a technical success rate of 92% with a minimal number of complications.

• Endovenous laser and radiofrequency obliteration (radiofrequency thermal ablation) are recommended for the elimination of reflux in perforating veins [188, 233].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. According to a systematic review, technical success in perforating vein obliteration using EVLA and RFA reaches 95% and 91%, and long-term occlusion rates reach 89% and 77%, respectively.

• Endovenous laser and radiofrequency obliteration are recommended for the elimination of reflux in intrafascial segments of superficial veins in recurrent varicose veins [300, 307, 308].

LE 4 GSR C

• Operations for chronic venous disease, including those using thermal vein obliteration technologies, are recommended to be performed in outpatient and/or inpatient facilities by cardiovascular surgeons and surgeons [309].

LE 4 GSR C

Comment. Currently, radiofrequency and laser obliteration are approved for use in Russia and are performed as part of primary specialized healthcare for adults in the "surgery" profile in outpatient or day-hospital settings by specialists holding a qualification in "cardiovascular surgery" or "surgery," regardless of the form and stage of the disease. Endovenous thermal obliteration may be performed in inpatient settings as part of specialized medical care for adults in the profiles of "surgery" and "cardiovascular surgery."

• When choosing between EVLA and RFA, neither thermal ablation method is recommended as preferred in patients with chronic venous disease [261–263, 310–312].

LRE 1, GR A

Comment. When compared with EVLA and RFA, both methods demonstrate equivalent efficacy in terms of achieving durable GSV occlusion; in some studies, EVLA was characterized by higher levels of postoperative pain and greater severity of intradermal bruising [199, 313–319]. It should be noted that the current evidence base includes results from early clinical studies using short-wavelength laser radiation, bare-tip fibers, and first-generation radiofrequency ablation catheters, and cannot be fully extrapolated to modern endovenous thermal ablation methods (long-wavelength laser radiation, flexible fibers with connectors and tips for medical laser units of Radial and 2ring types, ClosureFast catheter). According to modern RCT results using ClosureFast technology and a 1470 nm laser with a radial fiber, no fundamental differences in all outcomes—including postoperative pain, return-to-work time, complication rates, reduction of chronic venous disease severity, and quality of life improvement—were identified between the methods [320].

LE 2 GSR A

Comment. It has been shown that high ligation (crossectomy) combined with endovenous laser ablation (EVLA) of the great saphenous vein (GSV) trunk does not reduce the long-term risk of varicose vein recurrence (follow-up period up to 6 years) [321].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. The results of a systematic review with a meta-analysis of studies comparing the elimination of varicose veins simultaneously with truncal ablation or in a delayed manner demonstrate the advantage of a simultaneous approach in terms of reducing the need for repeat interventions (6.3% vs. 36.1%) and a more significant short-term improvement in quality of life, which, however, disappears during further follow-up [324]. This approach is attractive due to the reduced invasiveness and labor intensity of treatment, and a potential reduction in its cost; however, to date, there is insufficient data to identify a group of patients for whom this intervention tactic would be preferable. Individual studies demonstrate that complete and partial spontaneous reduction of varicose tributaries 6 months after isolated EVLA of the main saphenous veins is observed in 23% and 63% of cases [325].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment. There are no formal restrictions on the use of thermal ablation methods based on vein diameter. Tortuosity and large vein size, trunk duplication, or aplasia of trunk fragments, superficial subcutaneous location of the vein, its aneurysmal dilation, and the presence of multiple junctional tributaries are not absolute contraindications to endovenous methods. Such structural features of the venous system should be diagnosed before surgery, as they can significantly complicate the procedure, but with accumulated experience, they do not serve as a barrier to performing thermal ablation.

LNC 5 LeC C

Comment. There are a number of publications with significant limitations in data reliability addressing the possibility of performing thermal ablation in thrombophlebitis. However, convincing evidence of efficacy and safety is lacking. To date, there is no reliable data on the optimal timing for performing thermal ablation after previous superficial vein thrombosis. Time intervals ranging from the subsiding of the inflammatory process up to 3 months are considered [233,331].

The most up-to-date information on this issue is presented in the relevant clinical guidelines.

LNC 5 LeC C

LNC 5 LeC C

Comment. In such situations, the use of thermal ablation methods is possible if an assessment of the balance between individual treatment benefits and associated risks has been performed, with the expected individual benefit significantly exceeding the individual risk.

• In patients on long-term oral anticoagulants (ATC: B01, antithrombotic agents), performing EVLA and RFA is recommended without interrupting therapy [334–339].

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. Studies have shown high efficacy and safety of performing EVLA while taking direct oral anticoagulants (ATC: B01, antithrombotic agents) and vitamin K antagonists, achieving therapeutic INR values.

• When performing thermal ablation, it is recommended to perform ultrasound guidance at all stages of the surgery in patients with CVD [340].

LNC 5 LeC C

Comment. Ablation of healthy segments of the GSV and small saphenous vein (SSV), excluding short sections located distal to draining varicose tributaries, is undesirable due to the same reasons that limit total stripping of these veins.

• In the case of regional anesthesia or general anesthesia, it is recommended to create a "cuff" around the GSV or SSV trunk using sodium chloride** (similar to tumescent anesthesia) in patients with CVD [341].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. When performing thermal ablation, "hydro-isolation" of the vein from surrounding tissues is required, which consists of injecting an anesthetic solution (tumescent anesthesia). This provides anesthesia, external compression of the vein with a reduction in its diameter, and the maximum possible displacement of blood to ensure close contact of the vein wall with the thermal energy source and to reduce unwanted energy absorption by blood [342].

• For thermal ablation of the SSV, it is recommended to puncture the vein in the middle third of the leg and higher in patients with CVD [340,343,344].

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. Puncture of the SSV in the lateral malleolus region is associated with a higher incidence of paresthesias compared to puncture in the middle third of the leg [343]. At the same time, no effect of the puncture site on the rate of achieving stable occlusion of the target vein was identified [344].

• For EVLA, it is recommended to use "hemoglobin" or "water" lasers (Medical Device: surgical laser systems) [345–350].

LE 2 GSR A

Comment. "Hemoglobin" lasers (H-lasers) include lasers (Medical Device: surgical laser systems) with a wavelength close to 1000 nm (e.g., 810 nm, 940 nm, 980 nm). "Water" lasers (W-lasers) include lasers (Medical Device: surgical laser systems) with a wavelength close to 1500 nm (e.g., 1320 nm, 1470 nm). Recently, the use of lasers (Medical Device: surgical laser systems) with a wavelength close to 2000 nm has been expanding. There is one RCT comparing the results of EVLA using 1920 nm and 1470 nm lasers in 67 patients with a follow-up of up to 1 year. Differences in efficacy and safety were not significant [351]. Wavelength is an important, but not decisive, factor in the outcome of the intervention [352]. The energy regimen (linear energy density, power-to-exposure-duration ratio, radiation emission pattern (laser fiber type)) plays an equally important role in application efficacy, as well as the frequency and severity of side effects [345–349].

• When performing EVLA, it is recommended to prefer modern fiber types (fibers with radial (ring) emission) over end-fire emission fibers [353–359].

Leveled Research Evidence (LE) 2 Grade of Recommendation (GR) B

Comment. A disadvantage of the end-fire fiber is the uneven effect of laser radiation on the vessel wall, which leads to microperforations of the vein and damage to surrounding tissues, determining the development of postoperative complications and adverse reactions. The use of modern fibers is characterized by a low incidence of adverse reactions [353–358].

• For effective and safe ablation of the GSV trunk using "hemoglobin" lasers, it is recommended to use a linear endovenous energy density (LEED) of at least 80 J/cm and a radiation power of 15 to 25 W [360].

LE 3 GSR C

Comment 1. These recommendations are relevant provided that end-fire emission is used. The use of radial emission fibers with hemoglobin lasers is not advisable due to the high probability of carbonization of the working part of the fiber and, consequently, a decrease in efficiency [361].

Comment 2. EVLA uses two energy parameters. Linear endovenous energy density (LEED) is the amount of energy per 1 cm of vein length. Endovenous fluence equivalent (EFE) characterizes the energy flux per unit area. Linear energy density is calculated using the formula:

LEED (J/cm) = P (W) x t (sec)

where LEED is linear endovenous energy density (J), P is radiation power in W, and t is exposure time per 1 cm of vein. Exposure time is inversely proportional to the fiber pull-back speed and can be calculated as: t (sec) = S (m) / v (m/s). S is a fixed value, which is 1 cm of vein, or 0.01 m. The speed in modern automatic fiber pull-back devices is usually set in the range of 0.7-2 mm/sec. Thus, at a pull-back speed of 1 mm/sec, the exposure time per 1 cm of vein will be 10 sec, and the LEED will equal P (radiation power) x 10.

The following formula can be used to recalculate LED and EFE:

LED (J/cm) = π × EFE (J/cm2) × D (cm)

where D is the vein diameter in cm.

• For effective and safe ablation of the great saphenous vein (GSV) trunk using 1X-nm water-absorption lasers, it is recommended to use an LED of at least 60 J/cm and a laser power of no more than 15 W [360].

LE 3 GSR C

Comment. Increasing the laser power above 15 W with water-absorption lasers while maintaining the energy density does not lead to improved ablation outcomes, but is accompanied by a higher rate of adverse reactions [362,363]. At the same time, achieving the same LED value through various combinations of laser power and fiber pullback speed does not affect the vein occlusion rate or the severity of perioperative pain [364]. An increased energy delivery to the sub-ostial segment of the GSV compared to the calculated value is permissible [326,362]. Optimal energy regimens for lasers with a wavelength of approximately 2000 nm and for effective and safe ablation of the small saphenous vein (SSV) trunk have not yet been reliably established.

• The radiofrequency ablation catheter is recommended to be positioned immediately distal to the junction of the superficial epigastric vein, or 2 cm distal to the saphenofemoral junction (SFJ) if the superficial epigastric vein is not visualized [365].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment 1. It is believed that positioning the catheter at a distance of less than 2 cm from the SFJ may cause endothermal heat-induced thrombosis (EHIT).

Comment 2. The Closure/Venefit technology has been known since 1998 as the ClosurePLUS bipolar ablation catheter. This technology did not become widespread due to its complexity, duration, and high number of complications. In 2007, the ClosureFAST catheter (now Venefit) was introduced. The delivered power is regulated automatically via feedback through a thermal sensor in the working tip of the catheter, maintaining a constant catheter tip temperature of 120 °C during the treatment cycle. The occlusion rate is 94–98% at 12 months [366], 92.6% at three years [367], and 91.9% at 5 years [368]. RFiTT (Radiofrequency-induced thermotherapy) technology refers to radiofrequency-induced thermal bipolar ablation. A variable high-frequency current generator heats the tissues during catheter withdrawal in the range of 70–100 °C [369,370]. The search for optimal regimens for this procedure is ongoing; experimental studies have shown maximum efficacy with a 6 W regimen and catheter withdrawal of 0.5 cm every 6 s (LED 72 J/cm) [371]. The occlusion rate reaches 88.7% at 1 year [372]. EVFR technology represents radiofrequency-induced monopolar ablation (using a flexible plate electrode with a 5 mm tip). The technical efficacy of the method reaches 96% at one month and 89% at one year with a low complication rate [373], and does not differ from the Venefit technology at a 5-year follow-up regarding the occlusion rate (87.6% vs. 87.8%), varicose vein recurrence (10.3% vs. 12.9%), and chronic venous disease (CVD) severity according to VCSS [374]. Currently, the evidence base for the latter two technologies is insufficient [369]. It should be noted that international guidelines of various levels usually do not perform a separate analysis of the efficacy and safety of RFA modifications, grouping them under a single term despite significant differences in their mechanism of action on biological tissues. The recommendations proposed below are based on studies using the first technology; they should not be extrapolated to other RFA modifications.

• When performing radiofrequency ablation (radiofrequency thermal ablation), it is recommended to deliver two standard (20-second) energy cycles in the sub-ostial segment and one cycle along the course of the vein [365].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. There are a number of studies claiming the need to increase the number of energy cycles to improve procedure efficacy [375–377]. At the same time, other authors concluded that, provided standard procedure parameters are followed, the diameter does not affect the probability of achieving occlusion [378]. An increase in the number of standard energy cycles in the sub-ostial segment and along the vein is permitted depending on the characteristics of the treated vein (large diameter, local aneurysmal dilatations, inflow of large tributaries or perforating veins). The optimal vein diameter for RFA is recommended to be 2–20 mm, which does not exclude the possibility of ablating veins of larger diameters [365].

LNC 5 LeC C

Comment. Neurological disorders (paresthesia, hyperesthesia, hypoesthesia, anesthesia) occur as a result of thermal injury to the cutaneous branches of the sural nerve or saphenous nerve. Severe and prolonged neurological deficit is extremely rare. Extremely rare complications requiring treatment depending on the specific case include: infectious complications, endovenous device fragmentation (fiber tip retention) [379], acute cerebrovascular accident (reported in a single case in a patient with a confirmed patent foramen ovale) [380], and arteriovenous fistula formation [381–386]. Skin and subcutaneous tissue burns are exclusive complications of EVLA associated with an insufficient or absent insulating "sleeve" of saline or local anesthetic.

LNC 5 LeC C

Comment. Pain after EVLA is typically characterized by low to moderate intensity

• In type I endothermal heat-induced thrombosis (EHIT), it is not recommended to alter patient management tactics or record this finding in medical documentation as a complication [387,388].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. L. Kabnick's classification is the most widely used to describe endothermal heat-induced thrombosis [389]. This classification is available in Appendix A1. Type I EHIT represents superficial vein thrombosis up to the saphenofemoral junction ("thermal high ligation") and is frequently regarded as a positive surgical outcome. Studies demonstrate that this approach does not increase the risk of VTE [388]. Currently, there are no robustly proven risk factors for the development of endothermal heat-induced thromboses [252,390,391]. Thermal-induced thrombosis of the femoral or popliteal vein is the most characteristic variant of VTE following thermal ablation; however, it very rarely leads to pulmonary embolism (up to 0.03% with no reported fatal cases) and completely resolves within 4 weeks [251,392,393].

• In type II endothermal heat-induced thrombosis, it is recommended to perform active surveillance without pharmacotherapy, or administer antiplatelet agents (ATX: B01AC, platelet aggregation inhibitors excluding heparin) with weekly follow-up, or administer anticoagulants (ATX: B01, antithrombotic agents) with weekly follow-up [387].

LNC 5 LeC C

Comment. In published studies, acetylsalicylic acid** was used as an antiplatelet agent (ATX: B01AC, platelet aggregation inhibitors excluding heparin) in the treatment of endothermal heat-induced thrombosis. In type II EHIT, patients may be prescribed antiplatelet agents (ATX: B01AC, platelet aggregation inhibitors excluding heparin) or anticoagulants (ATX: B01, antithrombotic agents) (prophylactic or therapeutic doses) with weekly follow-up [387,394].

• In type III and IV endothermal heat-induced thrombosis, it is recommended to administer anticoagulant therapy [387,394].

LNC 5 LeC C

Comment. Patients should be monitored weekly, and therapy adjusted in case of thrombus retraction or regression. If type IV EHIT is detected, patient management according to the venous thrombosis treatment protocol [253] is recommended.

• Upon the detection of cyanoacrylate-induced thrombosis and other varieties of ablation-associated extension thrombosis, it is recommended to describe, classify, and manage patients in accordance with the guidelines for EHIT [233].

LNC 5 LeC C

NTNT obliteration (NTNT, non-tumescent non-thermal) refers to the use of cyanoacrylate glue-based mainline vein obliteration (CAVO) using a special medical adhesive (several adhesive compositions differing in formulation, physicochemical properties, polymerization rate, and delivery devices are available on the global market: «VenaSeal», «VariClose», «VenaBlock», while only the «VenaSeal» technique is registered in Russia), as well as modified scleroo obliteration with mechanical injury to the venous wall (globally represented by «ClariVein» and «Flebogrif» devices, which differ in the mechanism of venous wall injury and the type of sclerosant used, whereas only the «Flebogrif» technology is registered in Russia).

• Cyanoacrylate glue obliteration is recommended as an alternative to thermal ablation to eliminate reflux in superficial truncal veins in patients with varicose veins [261,395–397].

Level of Evidence 1, Grade of Recommendation B

Comment 1. Current systematic reviews and meta-analyses demonstrate comparable or superior technical efficacy of CAVO compared to EVLA and RFA at a medium-term follow-up of 1–2 years, with a similar impact on CVI severity and quality of life, alongside a reduction in postoperative pain intensity, the incidence of cutaneous nerve injury, and the risk of induration and hyperpigmentation compared to thermal ablation methods [261,395,396]. In one network meta-analysis, CAVO was identified as the best method for great saphenous vein trunk obliteration compared to EVLA, RFA, sclerotherapy, and open surgery in terms of the long-term occlusion durability and perioperative pain severity [261]. Among all CAVO techniques, «VenaSeal» is the most studied, demonstrating advantages over EVLA, RFA, microfoam sclerotherapy, sclerotherapy, and open surgery regarding technical success, postoperative pain, and complication risks. Meanwhile, another systematic review noted a lack of data on the efficacy of CAVO in large-diameter superficial veins (>10 mm) [397].

Comment 2. According to a systematic review, the most frequent complication of CAVO is phlebitis of the obliterated veins, with an incidence rate reaching up to 25% [398]. Rarer specific complications include immediate- and delayed-type hypersensitivity reactions, which may manifest as various allergic conditions—including several months post-procedure—subcutaneous granuloma, and endovenous glue-induced thrombosis (EGIT) [398,399].

Comment 3. The decision to perform CAVO should be based on an individual risk-benefit assessment, considering the advantages of the method and the probability of specific complications, including delayed allergic reactions. Patients with a low pain threshold who wish to avoid numerous injections, experience difficulties using compression hosiery, or have trophic disorders requiring obliteration of the great saphenous vein trunk on the calf may derive the maximum benefit.

Evidence level 1, grade of recommendation C

Comment 1. Available systematic reviews and meta-analyses show contradictory results. According to some data, MOCA has a technical efficacy comparable to thermal ablation methods, but is associated with lower perioperative pain intensity and a lower risk of cutaneous nerve injury [395,400]. Other systematic reviews demonstrate insufficient technical efficacy of MOCA compared to EVLA, RFA, CAVO, and open surgery [261,396]. The most studied method is «ClariVein», whereas data for «Flebogrif» are derived predominantly from non-comparative studies [401].

Comment 2. The decision to perform MOCA should be based on an individual risk-benefit assessment, taking into account the advantages of the method and its moderately lower technical efficacy. Maximum benefit may be gained by patients with a low pain threshold seeking to avoid multiple injections, particularly in the presence of trophic disorders requiring obliteration of the great saphenous vein trunk on the calf, provided there is no need for reliable long-term target vein occlusion.

3.4.4. Elimination of horizontal reflux

LNC 5 LeC C

Comment. An indication for eliminating perforating veins is solely the pathological reflux through them objectively registered by ultrasound scanning. Objective assessment of perforator competence is only possible via ultrasound scanning in the upright patient position. Therefore, the established practice of examining perforators with the patient in the horizontal position must be recognized as incorrect. Even when perforating vein incompetence is detected, the individual patient's disease course, perforator location, and its characteristics must be taken into account.

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. It is advisable to perform interventions on veins with a diameter greater than 3.5 mm and a reflux duration of more than 0.5 s, located in the area of open or healed venous ulcers (classes C5 and C6) [75,76,89,101,104]. According to experts, intervention on perforating veins in the area of trophic disorders is advisable in some cases at clinical class C4. In all other cases, the advisability of surgical intervention on perforating veins is questionable due to a lack of evidence supporting this approach. Eliminating perforating veins does not increase procedural efficacy: it does not alleviate symptoms, improve quality of life, or reduce the risk of recurrence in uncomplicated varicose veins [402–404]. At the same time, in patients with venous trophic ulcers, eliminating perforating reflux is associated with a high chance of skin defect healing, which is not always a direct reflection of correcting perforator reflux due to the combined nature of treatment in non-comparative studies [188,189].

• For the elimination of perforating veins in CVI, minimally invasive interventions are recommended: subfascial ligation using miniphlebectomy hooks (vein extractors), subfascial endoscopic perforator surgery (SEPS), sclerotherapy/obliteration, ultrasound-guided laser or radiofrequency ablation (radiofrequency thermoablation) [188,189,402,405–407].

Level of Evidence (LE) 2, Grade of Recommendation (GR) C

Comment. Besides the classical method of perforator ligation through an incision, two other options of open percutaneous dissection of incompetent perforating veins are distinguished. In the first case, after preliminary ultrasound mapping or under ultrasound guidance, the incompetent perforating vein is epifascially destroyed using a miniphlebectomy hook. The second option involves percutaneous ligation of the incompetent perforating vein using an absorbable ligature. In the presence of trophic skin changes, incisions in the affected area should be avoided. The use of thermal ablation methods has no limitations regarding the location of perforating veins, does not require treatment postponement due to edema, induration, or skin atrophy, and is feasible even in the presence of an active trophic ulcer. The rate of perforating vein occlusion after EVLA reaches 89% at a 1-year follow-up [188,406]. In a comparative study, thermal ablation of incompetent perforating veins in addition to GSV EVLA in patients with venous ulcers did not change the ulcer healing rate, but accelerated healing from 3.3 months (95% CI 2.5–4.1) to 1.4 months (95% CI 1.15–1.66) [405]. For EVLA, depending on anatomical features, end-fire and radial-emitting laser fibers of both standard and small calibers can be used [408]. Optimal energy modes and the technique for perforator EVLA have not yet been determined. RFA of perforating veins provides stable occlusion at the level of 77% at 1 year of follow-up [188]. The use of first-generation technology demonstrated an occlusion rate of 81% for perforating veins at 5 years of follow-up [407]. A specially designed stylet is used for perforating vein RFA. Overall, due to its low invasiveness, thermal ablation appears to be the most effective method for eliminating pathological reflux through perforating veins [409]. Indications for endoscopic subfascial perforating vein surgery (ESPS) have currently narrowed significantly; it should be used only when minimally invasive methods are ineffective or impossible to apply [410,411]. Open dissection of perforating veins (Linton-Felder procedure) for the division of incompetent perforating veins should not be used in chronic venous disease surgery due to its high invasiveness and the availability of alternative techniques.

3.4.5. Alternative (vein-sparing) minimally invasive treatment methods

Evidence level 1, grade of recommendation C

Comment. The CHIVA method includes various technical approaches applied to each patient individually, depending on the types of shunts detected during ultrasound examination [412–415]. The actions of the surgeon performing the CHIVA procedure are aimed at eliminating the escape points and preserving the re-entry points. To achieve "reflux fragmentation" along the GSV, the incompetent trunk is ligated at the saphenofemoral junction (or at the point where trunk reflux begins to form, e.g., at a thigh perforating vein) and below one of the perforators located distally to the incompetent GSV segment. Varicose tributaries of the GSV are ligated at their junction with the trunk; they may be either removed or preserved with the expectation of lumen reduction. Thus, drainage of the preserved GSV trunk in the distal direction is ensured; i.e., trunk reflux is preserved, but the entire volume of blood from the trunk is drained via the perforating vein [412]. The results of two RCTs indicate a lower recurrence rate of varicose veins in patients who underwent CHIVA compared to those who underwent conventional stripping [418,419]. These findings are supported by the results of a network meta-analysis of published RCTs [416]. A Cochrane review of four RCTs involving 796 participants has been published. Three RCTs compared CHIVA with stripping, and one compared it with compression therapy in patients with venous ulcers [420]. Data analysis confirmed a lower rate of recurrence and complications after CHIVA. Nevertheless, it was noted that all studies were of relatively low quality, and further comparative studies are required to confirm these findings.

Level of Evidence 2, Grade of Recommendation B

Comment. ASVAL involves the elimination of varicose GSV tributaries while preserving the incompetent trunk. In a significant number of patients, this leads to the disappearance of pathological reflux and a substantial reduction in the GSV diameter [422–424,426]. In a prospective study involving 67 patients 1 year after isolated removal of varicose tributaries, complete disappearance of GSV reflux was registered in 66% of cases. A significant reduction in the diameter of the saphenous vein was observed in 100% of cases. Recurrence within 1 year developed in 10.8% of patients, and over a long-term follow-up period of 5 years, this figure was 66.3% [427,428]. The possibility of restoring valve function in the GSV trunk was also demonstrated when performing sclerotherapy of varicose tributaries either alone or in combination with EVLA of perforating veins or direct segments of varicose tributaries at the junction with the trunk [429,430]. Furthermore, isolated sclerotherapy was associated with a high rate of spontaneous occlusion of the GSV trunk (up to 34%). A systematic review showed that 1 year after an intervention based on ASVAL principles, the rate of valve function recovery in a primarily incompetent GSV reaches 68%, while the varicose vein recurrence rate ranges from 0.5% to 13.5% [421]. The SAPTAP RCT demonstrated equivalent efficacy in terms of quality of life between isolated phlebectomy with subsequent potential GSV trunk ablation at 9 months if symptoms persisted, versus simultaneous truncal ablation and miniphlebectomy. Moreover, in the isolated tributary removal group, a repeat intervention with GSV trunk ablation was required in only 25.6% of cases, and the approach itself was found to be more cost-effective [425].

3.4.6. Removal (phlebectomy) of varicose subcutaneous veins

LE 2 GSR A

Comment. Phlebectomy of varicose superficial veins can be performed in combination with any method for eliminating pathological vertical or horizontal reflux, as well as an independent procedure in the absence of reflux.

• To eliminate varicose superficial veins, it is recommended to use specialized phlebectomy hooks (vein extractors) [432–436].

LNC 5 LeC C

Comment. In Russia, this technique is traditionally called "miniphlebectomy" or "microphlebectomy". The technique involves the use of specialized phlebectomy hooks (vein extractors) and the removal of varicose veins through skin punctures made with an 18G needle or a No. 11 scalpel blade following preoperative vein marking.

• Miniphlebectomy is a safe and effective technique, and it is recommended to perform it under local anesthesia [432–436].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Other methods (vein ligation, vein removal through separate incisions) are more invasive and lead to inferior outcomes.

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. Hematoma is a rare complication and usually resolves spontaneously with adequate compression. A puncture and evacuation of the hematoma may be performed at the discretion of the attending physician.

3.5. Recurrence of lower extremity varices

The causes of recurrent varicose veins include natural disease progression, neovascularization, residual veins, as well as a combination of these factors [438–440]. The most frequent causes of varicose vein recurrence related to treatment planning include:

• preservation of an incompetent GSV and/or SSV (except for cases where CHIVA and ASVAL methods are used);

• incompetent GSV and/or SSV tributaries that were intentionally left behind with the expectation that they would disappear, but were subsequently not eliminated while remaining dilated;

Technical causes of recurrence that occurred directly during the surgical procedure may include the following:

• leaving a stump and/or segment of the GSV and/or SSV with pathological reflux into tributaries (during high ligation/crossectomy);

• inadequate technique of endovenous thermal ablation methods due to protocol violations, leading to incomplete vein occlusion (including the use of low energy in endovenous methods, administration of an insufficient concentration and/or dose of the sclerosing agent).

Disease progression is considered to be:

• involvement of a new venous basin (GSV and/or SSV);

• varicose transformation of previously intact GSV and/or SSV trunks and/or their tributaries;

• formation of reflux in a previously competent perforating vein;

• neovascularization.

Varicose veins that persist during the treatment stages of an uncompleted course of invasive procedures are not considered recurrent.

LE 4 GSR C

LE 4 GSR C

Comment. Open surgical interventions aimed at eliminating recurrent or residual veins may present certain difficulties due to altered anatomy and the structure of surrounding tissues resulting from previous surgery. In addition, they are associated with an increased risk of complications, such as damage to adjacent vessels and nerves—manifesting as a high incidence of postoperative paresthesia—as well as a high risk of infectious complications [78,300,307,444]. Studies have shown that open surgery in patients with recurrent disease requires a larger volume of local anesthetic or necessitates longer general anesthesia when performed under local or general anesthesia, respectively [444]. Nevertheless, surgeries for recurrent varicose veins are a sufficiently effective treatment method. Given the aforementioned difficulties, such interventions should be performed in specialized vascular centers by experienced surgeons.

• In patients with symptomatic recurrent varicose veins, it is recommended to consider endovenous thermal ablation methods, ultrasound-guided foam sclerotherapy, open surgical interventions, or their combination for invasive treatment, depending on the type of recurrence, the size of varicose veins, patient preference, technical equipment, and the specialist's experience [233].

LNC 5 LeC C

LE 2 GSR A

Comment. The objective of thermal ablation methods is to eliminate pathological reflux from deep veins into superficial ones. The results of randomized clinical trials demonstrate equal efficacy of endovenous thermal ablation methods compared to open surgical interventions in correcting recurrence, with a lower complication rate for endovenous methods [300,307,308,444,445].

LE 4 GSR C

Comment. Sclerobliteration is applicable both for eliminating pathological reflux from deep veins into superficial ones and for treating recurrent varicosities. The use of thermal ablation methods to eliminate pathological reflux is not always possible due to excessive tortuosity of recurrent veins or lack of necessary equipment and experience. Sclerobliteration is easier to perform and allows for staged correction. Sclerotherapy can be used as an independent treatment method for recurrence or in combination with open surgery or thermal ablation [192,194,446,447].

LE 4 GSR C

Comment. When correcting recurrent varicosities, the elimination rate of pathological reflux in patients after isolated miniphlebectomy is comparable to the results in groups undergoing open and endovenous surgical methods. Nevertheless, isolated miniphlebectomy reduces the risk of postoperative complications, can be performed under local anesthesia, and is associated with a short rehabilitation period [448].

3.6. Venous trophic ulcers

Level of Evidence (LoE) 1, Grade of Recommendation (GoR) A

Comment. Compression therapy may be the only sufficient method for complete healing of a venous ulcer (VU). In an open ulcer with signs of edema, cellulitis, and pronounced exudation, preference should be given to multi-layer compression bandages made of short-stretch elastic bandages, or multi-component bandages combining short- and long-stretch elastic bandages; after inflammation subsides and exudation decreases, patients should switch to special compression knitwear of compression class 2-3. The use of single-layer and single-component high-stretch bandages is ineffective.

Level of Evidence (LE) 2, Grade of Recommendation (GR) A

Comment. The association of this pressure level with the chance of VU healing was first determined in a randomized controlled trial investigating the efficacy of a four-layer compression bandage [451]. The use of medical compression hosiery of classes 1, 2, and 3 helps reduce the recurrence rate of VUs, with a trend toward greater efficacy of higher compression classes. At the root of this, however, patient adherence to treatment is the main factor, which necessitates prescribing a lower compression class for certain patients. Two-layer compression knitwear with a high level of stiffness demonstrates the highest efficacy, where the combined compression of the two layers is 35-40 mm Hg (compression class 3). At the same time, many studies confirm the high efficacy of multi-layer bandaging in ulcer treatment, with a compression level also corresponding to 40 mm Hg, which can be considered an alternative to compression knitwear [452,453]. There is evidence that further increases in compression enhance efficacy [454].

LE 3 GSR C

Comment. Inelastic adjustable compression systems are devices for independent use by patients, which, depending on the degree of strap tension, provide varying levels of resting pressure and are also characterized by a high stiffness index that correlates with the initial pressure [456]. Their use in venous VUs is associated with accelerated healing, reduced treatment costs, fewer visits to medical institutions, and improved quality of life [455].

LNC 5 LeC C

Comment. Non-steroidal anti-inflammatory drugs (ATC: M01A, Anti-inflammatory and antirheumatic products, non-steroids) are used for venous ulcers accompanied by severe pain syndrome, which indicates damage to the fascia, tendons, and periosteum. They are usually prescribed as an injection solution or suppositories. Antihistamines (ATC: R06A, Antihistamines for systemic use) are prescribed when there is skin itching and other signs of allergic dermatitis or eczema, until they disappear completely. Indications for antibacterial therapy include signs of acute infectious soft tissue inflammation surrounding the trophic ulcer, or a high degree of its bacterial contamination in the presence of systemic inflammatory response syndrome. In the absence of a systemic response to the infectious-inflammatory process in the ulceration zone, preference should be given to local debridement of the purulent focus using antiseptic solutions, interactive dressings, and physical methods.

• Surgical debridement is recommended as the preferred local treatment method at the initial stage of venous ulcer debridement [457–459].

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment. Local treatment of venous leg ulcers is one of the main components of therapy. Debridement of venous ulcers refers to the conditioning of the wound bed by removing necrotic and bacterially contaminated tissue, fibrin deposits, foreign bodies, and infected wound exudate. Surgical debridement involves the removal of necrotic tissue and fibrin deposits using a scalpel, curette, scissors, Volkmann spoon, or laser in an operating room and/or inpatient/outpatient setting. It is considered the fastest and most effective method of ulcer debridement. A systematic review identified no randomized controlled trials (RCTs) evaluating the effect of surgical debridement on the chance of venous ulcer healing [460].

Evidence level 1, grade of recommendation C

Comment. It is advisable to use modern wound dressings adapted to the phase of the wound healing process, which create a balanced moist environment optimal for regenerative processes. The choice of specific therapeutic agents depends on the characteristics of the wound process and the condition of the tissues surrounding the trophic ulcer. The selection of a dressing requires mandatory consideration of the phase of the wound healing process and the degree of exudation. Types of dressings are presented in Table 5. A compression bandage must be applied over the wound dressing. According to the results of a systematic review and network meta-analysis, currently, there is insufficient data to determine the optimal method of local treatment for venous ulcers that affects the chance of their complete healing [461].

Table 5. Modern dressings used for the treatment of venous trophic ulcers

LE 3 GSR C

Comment. Modern antiseptics are ineffective in cleansing venous ulcers and exhibit cytotoxic effects.

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Level of Evidence (LE) 3, Grade of Recommendation (GR) B

Comment. Additional methods of local therapeutic impact on venous ulcers include laser irradiation, negative pressure wound therapy, biological debridement, and treatment in a controlled abacterial environment.

Every dressing change at any stage of treatment should include gentle cleansing of the venous ulcer, care for the surrounding tissues and, depending on the specific clinical situation, the application of modern wound dressings and/or topical medications. The frequency of dressing changes depends on the manifestations of the wound process (presence of necrotic tissue, amount and character of wound exudate, granulations, severity of epithelization, etc.). When treating the ulcer, jet irrigation of its surface with a sterile 0.9% sodium chloride** solution warmed to 37°C is considered optimal. The use of concentrated antiseptics (ATC: D08A, Antiseptics and disinfectants, povidone-iodine**, hydrogen peroxide**, etc.) traditionally used in the treatment of acute wounds should be avoided, as they not only destroy microorganisms but also exert a cytotoxic effect, damaging the granulation tissue. High-pressure lavage and whirlpool therapy are undesirable because they promote the penetration of microorganisms deep into the tissues and damage the microvasculature. Surgical debridement is performed in the presence of a large amount of necrotic tissue and fibrin. At the same time, the procedure should not aim to expose the base of the venous ulcer. Further local treatment depends on the phase of the wound healing process.

Negative pressure wound therapy (NPWT) helps improve treatment outcomes for complex venous ulcers and has led to a number of major changes in clinical practice over the past decade. NPWT should be used as part of an individualized comprehensive treatment plan. Its objectives are to remove exudate, reduce periwound edema, improve microcirculation, reduce ulcer size, optimize the wound bed, accelerate granulation tissue growth, and reduce the complexity of surgical wound closure procedures. Low-quality evidence suggests a positive effect of NPWT on the healing rate of lower extremity venous ulcers of various origins [463].

LRE 1, GR A

Comment. In selected cases, staged surgical interventions are permissible. The randomized clinical trial EVRA demonstrated that early elimination of superficial reflux by endovascular methods reduces the mean healing time of venous trophic ulcers from 82 (95% CI, 69–92) days to 56 (95% CI, 49–66) days and increases the chance of healing within 24 weeks by 1.4 times [468]. A systematic review with meta-analysis showed that performing endovenous ablation in addition to standard therapy increases the chance and reduces the healing time of the ulcer [467].

LNC 4 LeC C

Comment. Along with operations on the venous system, in cases of long-term non-healing ulcers with the development of severe soft tissue changes in the form of lipodermatosclerosis, layered excision of the ulcer along with altered tissues followed by skin grafting (shave therapy) is advisable. Split-thickness meshed skin autografts are used both as an independent method and in combination with interventions on the venous system.

3.7. Medical nutrition therapy for patients with lower extremity varices

The organization of therapeutic diet therapy for patients with lower extremity varicose veins during inpatient treatment in medical organizations is carried out in accordance with the orders of the Russian Ministry of Health No. 330 dated August 5, 2003 "On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation", No. 395n dated June 21, 2013 (registered by the Ministry of Justice of the Russian Federation on July 5, 2013, No. 28995) "On approval of therapeutic nutrition standards", and No. 1008n dated September 23, 2020 "On approval of the procedure for providing patients with therapeutic nutrition" [471–473].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

The procedure for developing and implementing an individual rehabilitation and habilitation program for a disabled person is approved and implemented in accordance with the Order of the Ministry of Labor and Social Protection of the Russian Federation No. 545n dated June 26, 2023 [474]. The scope and spectrum of rehabilitation measures can certainly vary. Nevertheless, it is necessary to outline the general principles of rehabilitation for patients and disabled individuals with CVD, which should be strived for in all cases.

The essence of the rehabilitation program is a set of measures aimed at reimbursing (compensating) lost (impaired) functions and activity limitations. The goal of the program is to improve the patient's quality of life. In CVD, these tasks are implemented through behavioral and lifestyle modifications, combined with an additional set of therapeutic and prophylactic medical measures.

LNC 5 LeC C

Comment 1. Since the development of chronic venous disorders (CVD) occurs under conditions of orthostatic load, one of the key tasks of rehabilitation measures is also to bring the individual daily orthostatic load into compliance with the capabilities of the affected venous system. An important component of rehabilitation is the attending physician's educational and pedagogical work aimed at a detailed inquiry into the patient's lifestyle, informing them about the disease and prognosis, as well as developing specific recommendations for modifying risk factors.

Comment 2. lifestyle modification (changing working conditions, increasing dynamic activity, dosed therapeutic walking, regular unloading gymnastics, swimming, postural drainage) can be accompanied by the alleviation of CVD symptoms. It is necessary to reduce continuous and total daily vertical load, occupational and domestic physical inactivity, physical overloads, excess body weight, as well as to eliminate bad habits and adverse circumstances. Lifestyle recommendations include daily walking, preferably in the middle of the day or before/after work (in compression hosiery if recommended by a physician); resting with elevated legs during breaks and whenever possible; elevation of the foot of the bed by 10-20 cm to achieve an angle of approximately 10 degrees, except for patients with chronic heart failure, pulmonary hypertension, peripheral arterial disease, and hiatal hernia; leg skin care (skin moisturization to prevent dryness and cracking); cold showers, especially during the warm season; wearing loose clothing that does not restrict movement and breathing; orthopedic correction for foot dysmorphism, comfortable low-heeled shoes (<3 cm) with insoles; avoidance of sunbathing, saunas, hot baths; weight control [475].

Comment 3. Obesity is a risk factor for the development of CVD and, possibly, varicose veins of the lower extremities [476–478]. Age and obesity are two major risk factors for cardiovascular disease; with the growing prevalence of obesity and increasing life expectancy of the population, a sharp increase in the burden of cardiovascular disease is expected [479,480]. In a study using duplex scanning, significant reflux was observed in patients with a higher BMI (P=0.006), with age and BMI positively correlating with the clinical class of CVD [477]. A retrospective cross-sectional study including 482 CVD patients revealed a significant positive correlation between BMI and CVD clinical classes for women (0.43), but not for men (0.07). Obesity (BMI ≥ 30.0) was significantly more frequent in CVD patients in clinical classes C3 (p <0.001) and C4 (p=0.002) and less frequent in CVD patients in clinical class C1 (p <0.001) [481]. A retrospective study on the effectiveness of surgical treatment of CVD evaluated by CIVIQ and VCSS analyzed the outcomes of surgeries in 65,329 patients (77% women; 23% men): significantly worse outcomes were noted in patients with a BMI ≥35 kg/m², and the worst outcomes in patients with a BMI ≥46 kg/m². Treatment outcomes regarding changes in CIVIQ and VCSS in patients with a BMI ≥46 kg/m² were so poor that the authors suggest considering weight loss before offering varicose vein treatment [482].

Comment 4. An essential reserve for patient rehabilitation, as well as for the prevention of the progression of lower extremity venous diseases, is the correct choice of profession and rational organization of labor in the chosen specialty. For example, during prolonged sitting, it is useful to periodically take unloading breaks with an elevated position of the lower extremities and use a foot exerciser placed under the office desk. Simple changes in working conditions, such as equipping workstations with high chairs, compliance with work and rest regimens, and medical consultations, can be very effective.

LNC 4 LeC C

Comment. Functional insufficiency of the muscle-vein pump (MVP) of the foot and calf due to decreased muscle strength, ankle range of motion (AROM), and walking speed plays an important role in increasing venous hypertension in CVD [483–485]. Therapeutic exercise (physical therapy) is recommended to address the problem of muscle pump dysfunction [487,488]. An increase in venous tone can be achieved through strength exercises to strengthen calf muscles and endurance exercises [475,488–490]. It has been established that isometric and isotonic calf muscle strengthening exercises in patients with venous ulcers lead to an increase in the muscle strength of the venous pump and AROM, resulting in a decrease in ambulatory venous hypertension [491,492]. A 12-week isokinetic exercise program in patients with chronic venous insufficiency (CVI) leads, along with an increase in MVP strength and AROM, to a reduction in pain and an improvement in quality of life [493]. In a double-blind RCT, it was found that an exercise program including aerobic exercise on a bicycle ergometer, strengthening and stretching exercises for the calf muscles, in addition to compression therapy, slowed the progression of CVI, reduced CVI symptoms and clinical severity, and improved the functional status and quality of life of patients [494]. A Cochrane systematic review on the use of exercise for treating CVI without ulcers included 2 RCTs, the quality of which was assessed by the authors as very low [486]. It was concluded that there is currently insufficient evidence to assess the effectiveness of exercise in CVI. At the same time, special water exercise protocols have been developed for patients with lower extremity venous diseases, including walking against a water current to increase venous return through calf muscle pumping [495]. Not only special physical therapy methods supervised by a physician are recommended, but also a set of simple exercises performed independently by the patient. It is advisable to introduce daily mandatory dosed walking and leg-unloading gymnastics. Swimming and aqua aerobics can be called the optimal type of sport for all forms of CVD and CVI. When choosing sanatorium-resort treatment, one should focus on the availability of therapeutic exercise, walking methods (terrain cure), and swimming [496].

Evidence level 1, grade of recommendation C

Comment. Balneotherapy (BT) includes various therapeutic procedures using mineral water (therapeutic contrast baths, therapeutic underwater shower-massage) and is carried out at thermal natural resorts as part of sanatorium-resort treatment for CVD. Movement in thermal water aims to restore MVP function, while hydrostatic pressure reduces venous edema. Underwater massage and Kneipp tracks (alternating hot and cold showers) stimulate the cutaneous vasomotor response, and underwater exercises can help with aggravating locomotor factors, including knee or ankle ankylosis [497]. Hydrostatic pressure acts on tissues and causes blood vessel compression, which can promote venous return and reduce edema and pain [497,500]. Underwater leg sonography has shown that water immersion reduces the diameter of normal and varicose veins, increases spontaneous blood flow, and reduces reflux if present [501]. Water warmth and buoyancy can block pain signals by affecting thermal and mechanoreceptors and increasing blood flow. There is also psychological relaxation associated with hydrotherapy, which contributes to pain reduction [502], and underwater exercises improve aggravating motor factors and restore MVP dysfunction [497]. Ankle strengthening has been shown to improve muscle endurance and may even restore proper muscle pumping function [475]. The role of water types with higher density is also noted [503]. The largest randomized controlled trial (RCT) to date on the use of BT in CVD showed that BT provides significant improvement in clinical symptoms and quality of life for people with advanced stages of CVI for at least one year of follow-up [504]. Based on a systematic review with meta-analysis, it was concluded that BT is able to slightly reduce the severity of CVD symptoms, possibly reduce the severity of hyperpigmentation, and improve quality of life, but does not affect the severity of edema and healing of venous ulcers [499].

Level of Evidence (LE) 5, Grade of Recommendation (GR) C

Comment. In addition to improving the hemodynamic state, physiotherapy methods aim to preserve or reactivate active and passive mechanisms regulating lower limb blood flow. The range of physiotherapeutic methods used for CVI with objectively proven efficacy is limited to various options of intermittent pneumatic compression (IPC), calf muscle electrical stimulation, pulsed magnetotherapy, and low-level laser therapy (LLLT).

Level of Evidence 2, Grade of Recommendation B

Comment. It has been established that IPC with a pressure of 120 mm Hg is effective for phlebolymphedema, helps reduce pain syndrome, improves venous blood flow, and promotes the healing of trophic ulcers [505–507].

LNC 4 LeC C

Comment. Modern electrical stimulation systems effectively activate the function of the calf muscle-vein pump regardless of the state of muscle tissue, surrounding joints, and the integrity of the venous valve apparatus, providing a significant increase in the linear and volumetric velocity of venous outflow. Calf muscle electrical stimulation can be used to relieve subjective and objective vein-specific symptoms, as well as part of the complex therapy of venous trophic ulcers [508–510].

Level of Evidence 2, Grade of Recommendation B

Comment. Based on the results of placebo-controlled RCTs, magnetotherapy has been shown to reduce pain syndrome and accelerate the healing of trophic ulcers of venous etiology compared to placebo controls. It has been established that the risk of recurrence in patients receiving a course of magnetotherapy is reduced by half compared to traditional conservative therapy [511–515].

Level of Evidence 2, Grade of Recommendation B

Comment. There is also fairly convincing evidence of the efficacy of LLLT in healing trophic ulcers of venous etiology. Various authors suggest using red (635–685 nm) or infrared (830–890 nm) laser radiation either as an external local exposure method or via intravenous laser irradiation (ILBI) (Low-Level Laser Therapy). In recent years, a method of combined laser exposure using radiation from various spectral ranges (ultraviolet [365–405 nm], green [525 nm]) has been developed, which improves tissue trophic support and reduces the severity of the inflammatory process. Despite the variety of methodological approaches, all researchers have established a statistically significant acceleration in the regeneration times of ulcer defects compared to control groups receiving traditional conservative therapy without LLLT [516–521]. Significantly less reliable evidence indicates the efficacy of low-intensity ultrasound therapy in healing trophic ulcers [522, 523].

5. Prevention and Dispensary Observation

According to Order No. 173n of the Russian Ministry of Health dated March 29, 2019, "On Approval of the Procedure for Dispensary Observation of Adults," medical check-ups (dispensarization) aim to detect chronic non-communicable diseases (and risk factors for their development) [524]. In patients with chronic venous diseases, prevention should target eliminating risk factors such as low physical activity, overweight, and lifestyle habits.

LNC 5 LeC C

Comment. In the absence of clinical manifestations of varicose veins, as well as in clinical classes C0–C2 of chronic venous diseases, the prevention of varicose vein development is not recommended due to the lack of data on methods with proven efficacy. The only effective measure to prevent the development of chronic venous insufficiency in patients with varicose veins is the timely elimination of the reflux source.

• For patients with C3–C4 chronic venous diseases associated with primary reflux in whom the reflux source cannot be eliminated, it is recommended to use elastic compression (A15.12.002 Lower limb elastic compression) of 20–30 mm Hg [115, 116].

Level of Evidence (LE) 3, Grade of Recommendation (GR) C

Comment. If timely surgical treatment is not feasible due to severe concomitant pathology in the patient or other reasons in the presence of lower limb varicose veins, the use of elastic compression is advisable to slow down the rate of disease progression as a measure to prevent complications [525, 526].

Evidence level 1, grade of recommendation C

Comment. Pregnancy can be considered a temporary risk factor for the development of lower limb varicose veins. It should be noted that although a number of large studies have found a direct correlation between the number of pregnancies and the severity of venous insufficiency in women predisposed to varicose veins [527, 528], some publications have questioned this relationship [529]. At the same time, there is no evidence of the efficacy of venoactive drugs or compression hosiery in preventing the appearance of varicose veins; therefore, the prophylactic prescription of medications or elastic compression to healthy women during pregnancy is impractical.

6. Organization of Medical Care

Medical care for patients with lower limb varicose veins can be provided in the following settings:

• outpatient (in settings not providing round-the-clock medical observation and treatment);

• in a day hospital (under conditions providing medical observation and treatment during the day, not requiring round-the-clock medical observation and treatment);

• inpatient (in settings providing round-the-clock medical observation and treatment).

Medical care for patients with lower limb varicose veins is provided in the following forms:

• primary health care;

• emergency medical care, including specialized emergency medical care;

• specialized medical care, including high-tech medical care.

Primary health care for patients with lower limb varicose veins includes:

1. primary pre-medical health care;

2. primary medical (physician-led) health care;

3. primary specialized health care.

Primary pre-medical health care is provided on an outpatient basis by mid-level medical personnel of feldsher health posts, feldsher-midwifery stations, medical outpatient clinics, health posts, polyclinics, polyclinic departments of medical organizations, medical prevention departments (offices), and health centers.

Primary medical health care is provided by a district physician or general practitioner (family physician) on an outpatient basis. Upon detecting signs of lower limb varicose veins, the patient is referred to a subspecialist for primary specialized health care.

Primary specialized health care is provided to patients with lower limb varicose veins by surgeons and cardiovascular surgeons. Ultrasound diagnostics physicians are engaged to perform diagnostic examinations. The ideal scenario is when a surgeon or cardiovascular surgeon has training in ultrasound diagnostics and performs the examination independently.

With the development of new medical technologies, including thermal and non-thermal ablation methods, sclerotherapy, and miniphlebectomy, the vast majority of patients with lower limb varicose veins can receive adequate surgical care on an outpatient basis.

Emergency, including specialized, medical care is provided to patients with lower limb varicose veins in the event of life-threatening conditions, such as bleeding from varicose veins or lower limb superficial vein thrombosis. In other cases, patients with lower limb varicose veins remain mobile and seek primary health care independently.

Specialized, including high-tech, medical care is provided in inpatient settings (day care) by surgeons, cardiovascular surgeons, and in some cases, endovascular diagnostic and treatment physicians. Ultrasound diagnosticians and radiologists may be involved in performing diagnostic examinations.

Indications for planned hospitalization of patients with lower limb varicose veins in a hospital include:

• surgical treatment of lower limb varicose veins when it is impossible (organizationally, logistically, or financially) to perform surgical treatment on an outpatient basis or in a day hospital setting;

• sanation of a venous trophic ulcer when it is impossible (organizationally, logistically, or financially) to perform treatment on an outpatient basis or in a day hospital setting;

Indications for emergency hospitalization of patients with lower limb varicose veins in a hospital include:

• bleeding from varicose veins when adequate medical care cannot be provided outside an inpatient setting;

• superficial vein thrombosis of the lower extremities with a high risk of thrombus extension to deep veins progressing to acute thrombophlebitis, when adequate medical care cannot be provided in an outpatient setting, or purulent thrombophlebitis;

• acute superficial vein thrombosis with clinical signs of inflammation reaching the upper third of the thigh in the great saphenous vein system and/or the upper third of the leg in the small saphenous vein system, when venous duplex ultrasound is not feasible;

Criteria for discharge from the hospital:

• completed surgical treatment of lower extremity varicose veins in accordance with a pre-established strategy;

• healing of a venous trophic ulcer, a stable tendency towards epithelialization of a trophic ulcer, or resolution of inflammatory signs in the area of a trophic ulcer, with no pronounced exudation or bleeding from the trophic ulcer;

• reliable hemostasis in case of bleeding from varicose veins, with no recurrence of varicose vein bleeding;

• no progression of the thrombotic process in superficial vein thrombosis, subsiding or tending to subside inflammatory signs, and appropriate anticoagulant therapy when indicated.

7. Additional Information

Not provided

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Apkhanova T.V., D.Sc. in Medicine, member of the Russian Society of Cardiology (RSC), member of the American Venous-Lymphatic Society (AVLS), member of the European Society of Cardiology (ESC); member of the National Association of Spa Treatment Experts

2. Bulatov V.L., Cand. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR);

3. Vakhratyan P.E., D.Sc. in Medicine, member of the Association of Phlebologists of Russia (APR), the Russian Society of Angiologists and Vascular Surgeons (RSAVS), and the Russian Society of Surgeons (RSS);

4. Volkov A.M., member of the Association of Phlebologists of Russia (APR);

5. Volkov A.S., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

6. Gavrilov E.K., D.Sc. in Medicine, member of the Executive Council of the Association of Phlebologists of Russia (APR);

7. Golovina V.I., Cand. of Sci. (Med.), member of the Association of Phlebologists of Russia (APR), Engagement working group International Union of Phlebology;

8. Derkachev S.N., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR), the Russian Society of Angiologists and Vascular Surgeons (RSAVS), the Russian Society of Surgeons (RSS), the National Association of Specialists in Thrombosis, Clinical Hemostaseology and Hemorheology (NATCHR), and the International Union of Angiology (IUA);

9. Efremova O.I., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

10. Zolotukhin I.A., Dr. of Sci. (Med.), Professor, Professor of the RAS, Executive Secretary of the Association of Phlebologists of Russia (APR);

11. Ivanov O.O., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

12. Ilyukhin E.A., Cand. of Sci. (Med.), Vice-President of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS);

13. Kalinin R.E., D.Sc. in Medicine, Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS), member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), and member of the Association of Cardiovascular Surgeons of Russia (ACSR);

14. Kamaev A.A., Ph.D. in Medicine, member of the Scientific Council of the Association of Phlebologists of Russia (APR), member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

15. Katelnitsky I.I., D.Sc. in Medicine, Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

16. Katorkin S.E., D.Sc. in Medicine, Professor, member of the Executive and Scientific Councils of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS), and member of the Association of Coloproctologists of Russia (ACR);

17. Konchugova T.V., D.Sc. in Medicine, Professor, member of the National Association of Spa Treatment Experts;

18. Kravtsov P.F., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS);

19. Kudykin M.N., D.Sc. in Medicine, Professor, Vice-President of the Association of Phlebologists of Russia (APR);

20. Kulchitskaya D.B., D.Sc. in Medicine, Professor, member of the National Association of Spa Treatment Experts;

21. Lobastov K.V., D.Sc. in Medicine, Associate Professor, member of the Association of Phlebologists of Russia (APR);

22. Maksimov S.V., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

23. Markin S.M., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

24. Mzhavanadze N.D., D.Sc. in Medicine, Associate Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR), member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

25. Parikov M.A., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

26. Pelevin A.V., member of the Association of Phlebologists of Russia (APR);

27. Petrikov A.S., Dr. of Sci. (Med.), Associate Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

28. Pikhanova Zh.M., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

29. Pryadko S.I., Ph.D. in Medicine, member of the Executive Council of the Association of Phlebologists of Russia (APR), Deputy Chairman of the "Phlebology and Lymphology" Section of the Association of Cardiovascular Surgeons of Russia (ACSR), member of the European Society for Vascular Surgery (ESVS) and the European Society of CardioVascular Surgery (ESCVS);

30. Rapovka V.G., D.Sc. in Medicine, Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

31. Rachin A.P., D.Sc. in Medicine, Professor, founder of the Russian Headache Society, President of the National Association of Comorbid Neurology Experts, member of the interregional society "North-West Pain Study Society";

32. Sapelkin S.V., D.Sc. in Medicine, member of the Executive Council of the Association of Phlebologists of Russia (APR); member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS);

33. Seliverstov E.I., D.Sc. in Medicine, member of the Executive Council of the Association of Phlebologists of Russia (APR);

34. Smirnov A.A., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

35. Stoyko Yu.M., Dr. of Sci. (Med.), Professor, Honored Doctor of the RF, Honored Scientist of the RF, laureate of the RF Government Prize, Honorary President of клиника Association of Phlebologists of Russia (APR), member of the Board of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), Honorary Member of the European Venous Forum (EVF);

36. Suchkov I.A., D.Sc. in Medicine, Professor, President of the Association of Phlebologists of Russia (APR), member of the Russian Society of Surgeons (RSS), member of the Russian Society of Angiologists and Vascular Surgeons (RSAVS), member of the Association of Cardiovascular Surgeons of Russia (ACSR), and member of the International Union of Angiology (IUA);

37. Tsaturyan A.B., member of the Executive Council of the Association of Phlebologists of Russia (APR);

38. Chabbarov R.G., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR);

39. Shevela A.I., D.Sc. in Medicine, Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

40. Shimanko A.I., D.Sc. in Medicine, Professor, member of the Executive Council of the Association of Phlebologists of Russia (APR);

41. Yakushkin S.N., Ph.D. in Medicine, member of the Association of Phlebologists of Russia (APR).

All members of the Working Group confirmed the absence of financial support or other conflicts of interest in the preparation of these guidelines.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

Target audience of the developed clinical guidelines:

1. Cardiovascular surgeon;

2. Surgeon;

3. Ultrasound diagnostics physician;

4. Medical students, residents, postgraduate students.

The recommendations are based on a cumulative analysis of evidence presented in global literature and obtained through the clinical application of modern principles and methods for diagnosing and treating lower extremity varicose veins. The main provisions of the Recommendations are ranked in accordance with Order No. 103n of the Ministry of Health of the Russian Federation dated February 28, 2019, "On approval of the procedure and timelines for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition, and scientific validity of the information included in clinical guidelines." The recommendations were prepared in accordance with the Methodological Recommendations for Assessing the Scientific Validity of Information Included in Clinical Guidelines, Center for Expertise and Quality of Medical Care of the Ministry of Health of the Russian Federation, 2019.

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for grading levels of evidence certainty (LEC) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Appendix A3. Reference Materials

Up-to-date instructions for the use of medicinal products are available on the official website of the Russian Ministry of Health at http://grls.rosminzdrav.ru (http://grls.rosminzdrav.ru/Default.aspx).

Appendix A3.1. Kabnick classification of heat-induced thrombosis

Type I – thrombotic occlusion reaching the saphenofemoral junction or saphenopopliteal junction;

Type II – extension of the thrombus into the deep vein with occlusion of no more than 50% of its lumen;

Type III - propagation of the thrombus into the deep vein with occlusion of more than 50% of its lumen; Type IV - propagation of the thrombus into the deep vein with complete occlusion of its lumen.

Appendix A3.2. Recommended methods for VTE prophylaxis according to individually assessed risk

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Varicose vein disease is a chronic, slowly progressive condition caused by a genetically determined weakness of the venous wall framework. At the same time, varicose veins are not a genetic disorder; environmental factors, primarily lifestyle, are required for its development. The onset and progression of the disease are associated with such triggering factors as prolonged static loads in a standing or sitting position, pregnancy, childbirth, obesity, etc. The incidence increases with age, although a significant number of cases are observed in individuals under 30 years of age.

Varicose veins may be the sole manifestation of chronic venous diseases or be accompanied by subjective symptoms: pain (aching, dull, nagging), sensation of pulsation, pulsating pain, tightness, constriction, heaviness in the legs, leg fatigue, feeling of swelling, cramps, skin itching, restless legs sensation, tingling, feeling of warmth or burning. Varicose veins are frequently accompanied by spider veins (telangiectasias) and reticular veins. These vascular elements are purely an aesthetic problem and are widespread even in the absence of varicose veins in healthy individuals. A complication of varicose disease is chronic venous insufficiency, which manifests as edema and trophic disorders, up to the formation of venous trophic ulcers.

Varicose vein disease is a steadily progressive condition that, in the absence of timely treatment, can lead to complications. It has been established that in the presence of varicose veins, the annual probability of new varicose veins appearing reaches 25%, the probability of edema and trophic disorders reaches 5%, the probability of a trophic ulcer is up to 1%, and the risk of thrombophlebitis is up to 1.3%.

Established varicose veins can only be eliminated by surgical removal, thermal or non-thermal ablation, or sclerotherapy. To date, there are no non-surgical methods to eliminate varicose veins. Any non-surgical treatment methods are aimed solely at relieving the subjective symptoms that may accompany varicose veins. The elimination of varicose veins is necessary to prevent further disease progression, reduce the risk of potential complications, improve appearance, reduce the severity of subjective symptoms, and improve quality of life.

Pathological blood reflux from deep veins into varicose subcutaneous veins leads to blood pooling (stasis) and subsequent volume overload of both superficial and deep veins. This promotes disease progression and complications. Therefore, eliminating the source of reflux and removing varicose veins are critical components of the treatment of varicose vein disease. The removal of subcutaneous veins cannot impair venous outflow function, since correct heart-directed blood flow is absent in the affected veins.

Various methods and combinations thereof can be used to eliminate sources of pathological blood reflux and varicose veins: surgical removal, endovenous laser ablation (EVLA), radiofrequency ablation (RFA), cyanoacrylate ablation (CAA), mechanochemical ablation (MOCA), and scleroblation (sclerotherapy). All methods are effective, and the choice of a specific treatment method is based on the physician's experience and preferences, as well as the medical facility's technical equipment. Unfortunately, no treatment method guarantees a lifetime result. Following surgery, the recurrence rate of new varicose veins reaches 30% after 3 years and 50% after 5 years. This is due to the persistence of genetically determined venous wall weakness and the ongoing impact of triggering factors. However, correctly performed treatment significantly reduces the risk of complications of varicose vein disease; in most cases, recurrence remains merely of cosmetic significance for a long time and can be eliminated with a minimally invasive procedure (scleroblation). Re-elimination of varicose veins can be performed an unlimited number of times throughout life.

Improvement of venous outflow function after surgical treatment generally leads to a reduction or complete disappearance of subjective symptoms. However, in some cases, complaints may persist postoperatively due to the systemic nature of venous wall involvement. In such situations, conservative therapy may be prescribed, including regular courses of venoactive drugs, medical compression hosiery, physiotherapeutic procedures (electrical stimulation of calf muscles), therapeutic exercise, etc. Unfortunately, none of the conservative treatment methods used in the postoperative period affect the risk of varicose vein recurrence.

Open surgery (combined phlebectomy, high ligation/crossectomy, stripping, miniphlebectomy) is usually performed in an inpatient setting, day surgery unit, or outpatient setting under local anesthesia, regional anesthesia, spinal anesthesia, or general anesthesia. The surgery consists of eliminating the main blood reflux pathways into the subcutaneous veins and addressing the varicose syndrome by exposing the veins through small incisions and/or removing them through skin punctures located along the course of the vein at various distances from each other. The number of incisions and skin punctures depends on the severity of varicose transformation. At the end of the procedure, skin incisions may be sutured or other wound edge approximation methods used, while skin punctures may be left unsutured. During the preparation for open surgery and after its performance, simple rules should be remembered:

1. Within 7-10 days before the surgery, you must undergo a preoperative examination prescribed by your surgeon. These are usually routine laboratory and instrumental diagnostic methods. The scope of the preoperative examination is determined by the internal regulations of a specific medical facility and may vary significantly.

2. If you are taking anticoagulants or antiplatelet drugs, be sure to inform your attending physician about this a week before the surgery.

3. Several weeks before the surgery, you may be prescribed venoactive medications at standard dosages to accelerate postoperative rehabilitation.

4. If the procedure is performed in an inpatient setting, you may spend several days there, so bring loose, comfortable clothing and comfortable shoes. You may use cotton underwear. Bring all the medications you are taking. If you wear glasses or use a hearing aid, you must bring them with you. Bring toiletries.

5. Check with your attending physician whether compression hosiery or elastic bandages are required for the surgery. Do not forget to bring them with you, as these items may be needed in the operating room immediately after the procedure.

6. You may be asked to shave your legs, groin folds, and perineum. In this case, it is necessary to shave your legs the day before the procedure. This issue is coordinated with the attending physician, as is the requirement to remove hair from the groin folds. Depilatory creams may be used instead of shaving. Do not apply oils, lotions, or creams to the operated limb within 24 hours prior to surgery. Take a shower on the morning of the surgery.

7. When undergoing surgery under spinal anesthesia or general anesthesia, have your last meal the evening before, and do not eat anything on the morning of the surgery. Clear liquids are usually permitted up to 2-4 hours before the surgery; however, you should confirm this with your attending physician or anesthesiologist. Consult your attending physician or anesthesiologist regarding whether you can take your regular medications on the morning of the surgery.

8. Follow the instructions of the surgeon and anesthesiologist after the operation.

9. Minor wound bleeding may occur during the first 12-24 hours after surgery. This is most commonly seen as small blood spots on the dressing or compression garments. There should be no significant soaking of the dressing or pads with blood, nor active leakage. You must report any such occurrences to your operating surgeon or a representative of the medical facility.

10. For several months, you may experience "thickenings", "indurations", or "lumps" in the surgical area, which will resolve on their own.

11. The first dressing change is usually performed the day after surgery, and subsequently as needed. The technique and frequency of dressing changes should be discussed with your operating surgeon.

12. The possibility and timing of taking a shower after surgery depend on the type of surgical wound closure. Consult your operating surgeon about this.

13. After surgery, you may be advised to use an elastic bandage or medical compression stockings for a specific period. You should discuss the duration of elastic compression therapy with your operating surgeon.

14. In the postoperative period, you may be prescribed venoactive drugs to accelerate rehabilitation. The dosing regimen and duration of the course are adjusted by your operating surgeon.

15. You may start walking as soon as the local anesthesia or general anesthesia wears off (as approved by the anesthesiologist-resuscitologist). Movements in the operated limb should be full range—flexion in the ankle and knee joints. You should not worry that something will happen while walking. Within the first month after surgery, you will return to your daily physical activities.

16. The ability to drive a car and engage in other activities requiring increased attention and concentration depends not only on the fact of the surgery, the bandage applied to the limb, but also on the medications used during the procedure. Consult your attending physician regarding when it is safe to resume such activities.

17. When planning surgery, you should arrange to avoid significant physical and/or static loads for 2-3 weeks after the procedure.

18. Follow all recommendations given by your operating surgeon.

19. Open surgical intervention may involve a number of adverse reactions and complications: pain (very common), ecchymoses (common), nerve injury (common), bleeding (rare), lymphorrhea and lymphocele (rare), wound infection (rare), deep vein injury (very rare), deep vein thrombosis (rare), pulmonary embolism (very rare), persistent neurological deficits (rare), chronic edema due to lymphatic vessel trauma (very rare). Consult your operating surgeon regarding the risk of complications and their consequences.

20. In cases where you develop signs of major bleeding, infectious complications (fever, redness in the area of postoperative wounds), pain in the calf muscles, lower extremity edema, retrosternal chest pain, shortness of breath, or any other disorders, seek medical help immediately from your operating surgeon or call emergency medical services.

Endovenous thermal ablation is a minimally invasive (incisionless) surgical technique that can be performed in an inpatient or outpatient setting under local anesthesia, nerve block, regional anesthesia, or general anesthesia. The goal of thermal ablation is to "seal" or "fuse" the vein from the inside, which stops blood flow through it and leads to its subsequent complete resorption. Trunk saphenous veins (great and small saphenous veins) and perforating veins are treated with thermal ablation. The objective of the treatment is to eliminate the reflux of blood from the deep venous system into the superficial system. At the same time, except for specific cases, visible varicose tributaries are not subjected to thermal ablation. To eliminate them, miniphlebectomy (removal of the vein through skin punctures using a specialized instrument) or sclerotherapy (injection of special substances into the vein causing them to "glue" together) may be additionally used. In some cases, after thermal ablation, varicose veins may completely collapse on their own, making targeted elimination unnecessary.

To perform thermal ablation, the target vein is punctured under ultrasound guidance, and a laser fiber or radiofrequency catheter is introduced into its lumen, advanced along the entire length of the vein, and positioned at its saphenofemoral or saphenopopliteal junction. Next, multiple injections of an anesthetic solution are administered around the vein to create a supportive "cushion" that ensures close contact between the vein wall and the heat source, while also protecting surrounding tissues from potential thermal injury. Upon completion of the preparation phase, the direct thermal treatment of the vein wall begins. During this period, the surgeon manually or with the aid of a specialized device slowly withdraws the fiber or catheter from the vein, thereby ensuring thermal treatment of the vessel along its entire length. Upon completion of the thermal ablation process, the procedure may be concluded, or a second stage aimed at eliminating varicose tributaries may be initiated. During the preparation for endovenous thermal ablation and after its completion, you should remember these simple rules:

1. Prior to the intervention, the operating surgeon must assess your health status and confirm the absence of contraindications to surgical treatment. This may require a series of routine laboratory and instrumental diagnostic tests, the number and nature of which are determined by your concomitant pathology, the scope of the planned intervention, and the intended type of anesthesia. You must inform your operating surgeon about any chronic internal organ diseases, infectious diseases (HIV infection, hepatitis B, C, syphilis, etc.), malignant neoplasms, and cardiovascular diseases.

2. Endovenous thermal ablation is in most cases performed under local anesthesia. Therefore, if you are allergic to local anesthetics (procaine**, lidocaine**) or have previously experienced adverse reactions during local anesthesia, be sure to inform your operating surgeon.

3. If you are taking anticoagulants or antiplatelet medications, be sure to warn your operating surgeon in advance.

4. Several weeks before the procedure, you may be prescribed venoactive drugs at standard dosages to reduce the risk and severity of adverse reactions (pain, ecchymoses, etc.).

5. Ask your attending physician if compression stockings are required for the surgery. Do not forget to bring them with you, as they may be needed in the operating room immediately after the procedure.

6. You must shave your legs the day before the procedure. Ask your attending physician whether hair removal in the inguinal folds is required. Do not use oils, lotions, or creams. Take a shower on the morning of the surgery.

7. When undergoing surgery under local anesthesia, you may have a light breakfast and drink water on the morning of the surgery.

8. When undergoing surgery under spinal anesthesia or general anesthesia, have your last meal the evening before, and do not eat anything on the morning of the surgery. Clear liquids are usually permitted up to 2-4 hours before the surgery; however, you should confirm this with your attending physician or anesthesiologist. Consult your attending physician or anesthesiologist regarding whether you can take your regular medications on the morning of the surgery.

9. The duration of the operation depends on the individual anatomy of the venous network and the chosen method for eliminating varicose tributaries. Performing a miniphlebectomy after the completion of thermal ablation increases the overall duration of the intervention.

10. When undergoing the procedure under local anesthesia, you will remain active. Immediately after surgery, you may be recommended to take a 20-40 minute walk. Movements in the operated limb should be full range—flexion in the ankle and knee joints. You should not be afraid that something will happen while walking.

11. When undergoing the procedure under spinal anesthesia or general anesthesia, you will be able to walk as soon as the anesthesia wears off, in agreement with the anesthesiologist-resuscitologist.

12. During the first 24 hours after surgery, you may notice dampness on the dressing or compression stocking around the anesthesia injection site, which is the result of the injected solution leaking out through the skin punctures. There is no need to be concerned about this.

13. Due to the absence of surgical wounds, you may take a shower the day after the procedure. If an additional miniphlebectomy or sclerotherapy was performed, the possibility of water procedures should be discussed with your operating surgeon.

14. You can return to your work and daily activities almost immediately after surgery. The possibility of engaging in work associated with prolonged static loads or heavy physical exertion, as well as sports, should be discussed with your operating surgeon. When planning the surgery, you should arrange for the possibility of avoiding significant physical and/or static loads for 2–3 weeks after the procedure.

15. The ability to drive a car and engage in other activities requiring increased attention and concentration depends not only on the fact of the surgery, the bandage applied to the limb, but also on the medications used during the procedure. Consult your attending physician regarding when it is safe to resume such activities.

16. After surgery, you may be advised to use an elastic bandage or medical compression stockings for a specific period. You should discuss the duration of elastic compression therapy with your operating surgeon.

17. During the first week after surgery, you may experience low-to-moderate intensity pain in the surgical area. If you experience severe discomfort that limits daily activities or interferes with deep sleep, you may use medications to relieve the unpleasant sensations. Consult your operating surgeon regarding the preferred type of pain relief medication.

18. For a month, you may experience sensations of pulsation, a feeling of fullness, or mild pulling pain along the course of the obliterated vein, which is a normal manifestation of its resorption process. There is no cause for concern.

19. In the postoperative period, you may be prescribed venoactive drugs to help reduce the severity of undesirable consequences from the procedure. The dosage regimen and duration of the course are managed by your operating surgeon.

20. Follow all recommendations given by your operating surgeon.

21. During endovenous thermal ablation, a number of adverse reactions and complications may occur: pain syndrome (common), intradermal hemorrhages (very common), hematoma (rare), nerve injury (common), skin burns (extremely rare), superficial thrombophlebitis (common), hyperpigmentation (common), deep vein thrombosis (very rare), thermally induced deep vein thrombosis (rare), pulmonary embolism (very rare), acute cerebrovascular accident (extremely rare), and arteriovenous fistula formation (extremely rare). Consult your operating surgeon regarding the risk of complications and their consequences.

22. In cases where you develop signs of bleeding, infectious complications (fever, redness in the area of the surgical wounds), pain in the calf muscles, lower extremity edema, retrosternal pain, shortness of breath, or any other problems, seek help from your operating surgeon or call emergency medical services.

Non-thermal vein ablation techniques (mechanochemical and cyanoacrylate glue ablation) are minimally invasive surgical procedures performed in inpatient or outpatient settings, which do not require local or general anesthesia. Their goal is to "seal" the lumen of the superficial vein, which is achieved using a special adhesive in glue ablation, or by injecting a sclerosant with preliminary mild mechanical damage to the inner lining of the vessel in mechanochemical ablation. As a rule, main superficial veins (great and small saphenous veins) are subjected to ablation. The treatment objectives are similar to those of endovenous thermal ablation.

1. For non-thermal methods, the target vein is punctured under ultrasound guidance, and a glue delivery catheter or a special catheter with cutting blades is inserted into its lumen, advanced along the entire length of the vein, and positioned at its junction (ostium). Next, by injecting the glue and applying subsequent compression with the ultrasound probe or the surgeon's hand, a tight seal of the vessel is achieved. In mechanochemical ablation, cutting blades consisting of small thin wire protrusions are deployed at the vein ostium, and the instrument is pulled through the vein with the simultaneous delivery of a foamed sclerosant. The cutting blades are closed before extracting the catheter from the vein.

2. The preparation period for non-thermal procedures and the postoperative period are similar to those of endovenous thermal procedures and require compliance with simple rules:

3. In the preoperative period, the patient's condition is assessed, and necessary examinations and diagnostic procedures are performed.

4. The techniques do not require the mandatory use of anesthetics; however, if you have a drug allergy (especially to procaine**, lidocaine**), or have experienced adverse reactions during procedures and surgeries involving local anesthesia, be sure to inform your operating surgeon.

5. Notify your physician about the medications you are taking.

6. A few days before the procedure, venoactive drugs may be prescribed to reduce the risk of adverse reactions (hematomas, pain syndrome, etc.).

7. Check with your attending physician whether the use of compression hosiery or elastic bandages is planned after surgery. Their use is not always required for such procedures. Do not forget to bring your compression garments with you; they will be needed immediately after the procedure is completed.

8. The procedures do not require mandatory shaving of the leg before surgery. Do not use oils, lotions, or creams. Take a shower on the morning of the surgery.

9. You may have a light breakfast 1–2 hours before surgery, and drinking water is permitted; refrain from food and water for 20–30 minutes immediately before the procedure.

10. As a rule, non-thermal surgeries are short, but in each individual case, the duration depends on the anatomical features and the scope of work with varicose tributaries.

11. The surgery will not significantly reduce your mobility; upon completion, you may be recommended a 20–40 minute walk. Maintain full range of motion in the ankle and knee joints.

12. During the first 24 hours, discharge of serous and bloody fluid from the access sites and dampening of the applied dressing or compression stocking are possible. This is not dangerous and does not require special dressing changes.

13. You may take a shower the day after surgery. If serous discharge from the surgical access persists, you may use an adhesive bandage. If you are allergic to adhesive tape, use a bandage.

14. After surgery, you will be able to return to daily activities and work. The possibility of prolonged static or intense physical exertion, as well as sports, should be discussed with your attending physician. Take into account the possibility of restricting intense exertion for 2–3 weeks when choosing the date for surgery.

15. The surgery does not affect concentration and does not restrict your ability to drive a vehicle. Restrictions on the use of additional medications may apply; check this fact with your attending physician.

16. In the postoperative period, you may be advised to use compression hosiery or elastic bandages. As a rule, the duration of use is limited to one to two weeks of daytime wear, and round-the-clock wear for the first 24 hours. The duration of compression use depends on the adopted protocol for preventing adverse events, the scope of the procedure, and whether tributary vein sclerotherapy was performed.

17. In the postoperative period, mild pain in the intervention area, sensations of pulsation, and pulling sensations along the course of the vessel perceived as a "cord" may occur. To reduce the severity of these symptoms, the attending physician may suggest the use of anti-inflammatory drugs.

18. In 1–3 weeks, pigmentation—a light brown skin discoloration—may appear in the projection of the target vein. Such changes usually disappear on their own at various intervals from 2–3 months to a year and do not require additional therapeutic procedures.

19. In the postoperative period, you may be prescribed venoactive drugs to reduce the severity of adverse consequences of the procedure. The dosage regimen and duration of the course are managed by your attending physician.

20. Follow all recommendations given by your operating surgeon.

21. During non-thermal surgeries, a number of adverse reactions and complications may occur: pain syndrome (common), intradermal hemorrhages (common), hematoma (rare), superficial thrombophlebitis (phlebitis) (common), phlebitis-like reactions (rare), hyperpigmentation (common), deep vein thrombosis (very rare), glue prolapse (extrusion) into deep veins (very rare), nerve injury (very rare), pulmonary embolism (very rare), acute cerebrovascular accident (extremely rare), and arteriovenous fistula formation (extremely rare). Consult your attending physician regarding the risk of complications and their consequences.

22. In case of complications, seek help from your operating surgeon or call emergency medical services.

Sclerotherapy (phlebosclerosis, scleroablation) is a method of removing varicose veins consisting of the injection (using a syringe and needle) of special sclerosant drugs into their lumen. The method belongs to minimally invasive (incision-free) treatments for varicose vein disease.

Sclerosing agents (or sclerosants—specially developed alcohol-based substances) intended for intravenous administration. Sclerosants cause destruction of the inner (endothelial) layer of the vein and its significant narrowing, which creates conditions for sclerobliteration (glued adhesion) and complete closure of the venous vessel. The drug, its concentration, and volume are selected individually by the physician for each patient. When used correctly, the sclerosant causes only a local effect, and its systemic toxic effect on the body is excluded. If a small amount of sclerosant enters the deep venous system, it undergoes rapid dissolution (blood flow in deep veins is much higher than in superficial ones) without local or systemic damaging effects. Immediately after the action of the sclerosant, a specific thrombus («sclerothrombus», «coagulum») is formed in the lumen of the vein, as a result of which the vessel becomes dense and slightly painful. Next, the process of vein resorption begins, which can take 2–6 months, during which a thin connective tissue cord is formed and practically completely disappears in 1–1.5 years. Usually, sclerotherapy sessions are performed once a week. The duration of treatment depends on the stage and form of the disease and is determined by the attending physician. A positive cosmetic result of treatment appears no earlier than 2–8 weeks after the end of sclerotherapy.

To eliminate varicose veins, various types of sclerotherapy and their combinations can be used: liquid and foam sclerotherapy, ultrasound-guided sclerotherapy, and catheter-assisted sclerotherapy. Varicose tributaries, the trunks of the great and small saphenous veins, and perforating veins can undergo sclerotherapy. The type and method of sclerotherapy are determined by the attending physician. The sclerotherapy procedure consists of puncturing a vein with a needle of various diameters, depending on the caliber of the vessel, and intravascular administration of the drug. The procedure may be slightly painful, but does not require special anesthesia. During drug administration, tingling and burning sensations along the course of the vein may be observed. The number of injections per session is determined individually based on the degree of the lesion and the maximum allowable amount of the drug. In some cases, catheter-assisted sclerotherapy may be used. In this case, a special catheter is inserted into the vein lumen through a skin puncture under ultrasound guidance, through which the sclerosant is delivered. During drug administration, the catheter is moved along the vein, ensuring full contact of the agent with its wall throughout its length. Sometimes, the sclerotherapy procedure may be accompanied by surrounding the vein with a special injection of a solution to ensure closer contact of its inner lining with the sclerosing agent.

During the preparation period for sclerotherapy and after its performance, you should keep in mind simple rules:

1. Sclerotherapy is a safe treatment method with a minimal number of contraindications; therefore, preparation for it usually does not imply additional diagnostic methods. However, in some cases, the attending physician may need additional information about your health status and may prescribe a number of laboratory and instrumental tests.

2. Foam sclerotherapy is hazardous for individuals with congenital heart defects accompanied by right-to-left blood shunting (e.g., patent foramen ovale in the atrial septum). If you have a confirmed heart defect or previously noted the appearance of neurological symptoms (double vision, visual field defects, speech disorders, migraine-like headaches) during sclerotherapy, be sure to inform your attending physician about this. Such phenomena are not necessarily a contraindication to repeated sclerotherapy, but must be taken into account by the attending physician.

3. If you are taking anticoagulants or antiplatelet agents, be sure to inform your attending physician.

4. Of great importance is the intake of hormonal drugs (hormonal contraceptives, hormone replacement therapy drugs, agents for treating hormone-dependent tumors), drugs for treating alcohol dependence (, disulfiram), and antibiotics (minocycline). Be sure to discuss these issues when planning sclerotherapy.

5. Immediately after the procedure, a bandage of elastic bandages and/or medical compression hosiery will be applied to your leg. Depending on the form of the lesion and the type of sclerotherapy, you will need to use compression around the clock or daily for a specified period of time. Check with your attending physician regarding the elastic compression regimen (when you can first remove the bandage or stocking and wash your leg, how long it is necessary to sleep in compression, and for how long to use it continuously) and strictly follow their instructions.

6. Immediately after the procedure, you will be recommended a 30–40 minute walk. Pay due attention to this walk, as it is necessary for the full evacuation of the drug from deep veins and to prevent the formation of blood clots in them. During the walk, you should fully bend your leg at the knee and ankle joints and contract the calf muscle.

7. In rare cases, patients with a large volume of varicose vein lesions experience a feeling of mild malaise and/or dizziness during the first 24 hours after sclerotherapy, and body temperature rises to 37–38 ^°C. These health changes quickly pass after taking nonsteroidal anti-inflammatory drugs (ATC: M01A, anti-inflammatory and antirheumatic products, non-steroids) (e.g., acetylsalicylic acid**, ibuprofen**). In case of dizziness, you need to sit or lie down for a few minutes. All changes in well-being during the course of sclerotherapy must be reported to your attending physician.

8. The first time after removing the compression bandage or medical hosiery, you may discover hemorrhages in the area of performed injections, skin darkening, and the presence of swollen and painful veins. These reactions are a typical consequence of sclerotherapy, so you should not be afraid of them.

9. Indurations, mild soreness, and skin darkening along the course of varicose veins may persist for several months.

10. If you have dry skin or skin irritation from elastic bandages, you should lubricate your legs after washing with any nourishing cream convenient for you.

11. If you develop edema in the ankle joint area or pain, a feeling of «fullness» in the leg (during the first day after the sclerotherapy session), you need to remove the bandage, straighten all bandage folds and, if recommended by the attending physician, completely re-bandage the leg, but no earlier than 2 hours after the session. Then, it is advisable to walk for 30–60 minutes. When using medical compression hosiery, such situations rarely occur.

12. Compression garments must be changed regularly. The frequency of their replacement is determined by the manufacturer, so follow the official instructions in this matter. With round-the-clock use of hosiery, it is convenient to have two sets of compression garments.

13. For the entire treatment period, the physician may not recommend hot baths, bathhouses, saunas, any other thermal and sun procedures (including solariums), as well as «warming» ointments, compresses; leg massage; heavy physical activity (weight training machines); lifting heavy objects, carrying heavy bags. Treat these restrictions with care.

14. To reduce the severity of adverse reactions of sclerotherapy, you may be recommended to take phlebotropic drugs in standard dosages during the period of sclerotherapy.

15. Clarify with your attending physician the need to remove the compression bandage or medical hosiery before the next sclerotherapy session.

16. During sclerotherapy, a number of adverse reactions and complications may occur: allergic reactions (extremely rare), deep skin necroses (extremely rare), superficial skin necroses (rare), hyperpigmentation (frequent), secondary telangiectasias (frequent), nerve damage (extremely rare), respiratory disorders: inspiratory difficulty, chest heaviness, cough, raw feeling, burning sensation in the respiratory tract (frequent), neurological disorders: migraine-like pain, visual and speech disturbances (rare), transient ischemic attacks and cerebrovascular accidents (extremely rare), superficial vein phlebitis (rare), symptomatic deep vein thrombosis and pulmonary embolism (very rare). Consult your attending physician about the risk of complications and their consequences before starting treatment.

17. In cases where you develop signs of bleeding, infectious complications (fever, redness in the area of the surgical wounds), pain in the calf muscles, lower extremity edema, retrosternal pain, shortness of breath, or any other problems, seek help from your operating surgeon or call emergency medical services.

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

Appendix G1. VCSS (Revised Venous Clinical Severity Score, rVCSS) – CVI Severity Assessment Scale

Original title - Revised Venous Clinical Severity Score

Source (official developer website, validation publication): http://www.veinforum.org/wp-content/uploads/2019/05/Revised-VCSS-AVF.pdf

Type - assessment scale

Purpose: The scale was developed by a special committee of the American Venous Forum in 2000 (revised in 2010) as an adjunct to the CEAP classification and serves as a tool for assessing the patient's condition during dynamic follow-up.

Content: The scale presents ten main signs of CVI, the severity of each being scored from "0" – complete absence of symptoms, to "3" – maximum severity of symptoms.

Interpretation: The results are presented as the sum of all scores, with a maximum score of 30 and a minimum score of 0.

Appendix G2. CIVIQ questionnaire for assessing the quality of life of a patient with chronic venous disease [110]

Original title: The Chronic Venous Insufficiency quality of life Questionnaire

Source (official developer website, validation publication): https://www.civiq-20.com/

Type: questionnaire

Purpose: The CIVIQ questionnaire is a vein-specific questionnaire designed to assess the quality of life in patients with chronic venous disease.

Content: The questionnaire consists of twenty questions, each offering five response options depending on the severity of the symptom (from 1 – "mild" to "5" – "maximum possible").

Interpretation: The quality of life assessment result using CIVIQ-20 is presented as a Global Index Score (GIS).

For the questionnaire, the following are calculated: S – sum of scores; m – minimum theoretical sum of scores with minimum scores for each question; M – maximum theoretical sum of scores with maximum scores for each question.

Global Index Score = (S - m) / (M - m) × 100

Appendix G3. SF-36 Questionnaire for assessing the quality of life of a patient with chronic venous disease [109]

Original title - SF-36 Health Status Survey

Source (official developer website, validation publication): Ware J.E., Snow K.K., Kosinski M., Gandek B. SF-36 Health Survey. Manual and interpretation guide // The Health Institute, New England Medical Center. Boston, Mass. - 1993.

Type: questionnaire

Purpose - SF-36 is a generic questionnaire for assessing quality of life. The Russian translation and approbation of the methodology were carried out by the "Institute of Clinical Pharmacology Research".

Content (template): The 36 questionnaire items are grouped into eight scales: physical functioning, role-functioning, bodily pain, general health, vitality, social functioning, emotional state, and mental health. The scores for each scale range from 0 to 100, where 100 represents optimal health; all scales form two summary measures: mental and physical well-being.

Key (interpretation): Results are presented as scale scores ranging from 0 to 100, constructed in such a way that a higher score indicates a higher level of QoL.

1. In general, would you rate your health as (circle one number):

2. Compared to one year ago, how would you rate your health in general now (circle one number):

3. The following questions are about activities you might do during a typical day. Does your health now limit you in these activities? If so, how much? (circle one number on each line):

4. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities as a result of your physical health (circle one number on each line):

5. During the past 4 weeks, have you had any of the following problems with your work or other regular daily activities as a result of any emotional problems (such as feeling depressed or anxious)? (circle one number on each line):

6. During the past 4 weeks, to what extent has your physical health or emotional problems interfered with your normal social activities with family, friends, neighbors, or groups? (circle one number):

7. How much bodily pain have you had during the past 4 weeks? (circle one number):

8. During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the home and housework)? (circle one number):

9. These questions are about how you feel and how things have been with you during the past 4 weeks. For each question, please give the one answer that comes closest to the way you have been feeling (circle one number):

10. During the past 4 weeks, how much of the time has your physical health or emotional problems interfered with your social activities (like visiting friends, relatives, etc.)? (circle one number):

11. How TRUE or FALSE is each of the following statements for you?

Appendix G4. Caprini Scale for assessing the risk of venous thromboembolism in surgical patients [531].

Original title: Caprini score (Caprini Risk Assessment Model)

Source (official developer website, validation publication): Gould M.K., Garcia D.A., Wren S.M., Karanicolas P.J., Arcelus J.I. Heit J.A., Samama C.M. Prevention of VTE in Nonorthopedic Surgical Patients. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. // Chest. 2012 -141: e227S–e277S.

Type: scale

Purpose: The Caprini scale is used as a risk stratification model for venous thromboembolism in surgical patients.

Content (template): Risk assessment is performed based on multiple parameters (age, mobility, body mass index, duration of surgery, presence of cardiovascular and blood disorders, family history of thromboembolism, and others), with each parameter assigned a specific number of points (1–4).

Key (interpretation): Results are presented as the sum of points obtained. VTE risk grading by points according to ACCP 2012: 0–1 point – very low (0.5%); 2 points – low (1.5%); 3–4 points – moderate (3%); >5 points – high (6%).