European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs

Guideline Writing Committee

Members of the Guideline Writing Committee (GWC) were selected by the ESVS to represent clinicians involved in the treatment of CVD and included vascular surgeons, vascular physicians, an interventional radiologist, and a gynaecologist – obstetrician. All members of the GWC were involved in selecting and rating the evidence for each of the different chapters and subsections under their responsibility (see Appendix with Supplementary Table of topics, search terms, and responsible authors), as agreed in the introductory meeting. All GWC members were involved in formulating the final recommendations.

GWC members have provided disclosure statements regarding all relationships that might be perceived as real or potential sources of conflicts of interest. These are filed and available at the ESVS headquarters. GWC members received no financial support from any pharmaceutical, device, or surgical industry to develop these guidelines.

Workflow for producing the guidelines

The GWC held an introductory meeting in November 2019 in Amsterdam, Netherlands, at which the list of topics and author tasks were determined. Contributions from GWC members were compiled into a draft of the guidelines by the chair and co-chair. After the first draft was completed and internally reviewed, the GWC met again in September 2020 in Frankfurt, Germany, to review and approve the wording of each recommendation. The guidelines then underwent three rounds of external reviews, and appropriate revisions were implemented.

Literature search

GWC members agreed on a common systematic literature search strategy for each of the chapters. A comprehensive literature search of articles published was performed using MEDLINE (through PubMed), Embase, Cardiosource Clinical Trials Database, and the Cochrane Library databases between 1 January 2013 and 30 June 2020, for relevant papers published in English. The search terms used for the different chapters and subsections are mentioned in the Appendix (Supplementary Table). Reference checking and manual search by the GWC members added other relevant literature. Only peer reviewed, published literature and studies presenting pre-defined outcomes were considered. The selection process followed the “pyramid of evidence”, with aggregated evidence at the top of the pyramid (meta-analyses of several randomised controlled trials [RCTs], other meta-analyses, and systematic reviews), followed by RCTs and finally observational studies. Single case reports, abstracts, and in vitro studies were excluded, leaving expert opinion at the bottom of the pyramid. Articles published after the search date or in another language were included only if they were of paramount importance to this guideline. After the first and second external review, the members of the GWC performed a second and third literature search within their area of responsibility to determine if any important publications had been published between July 2020 and February 2021, and further until the end of June 2021, respectively.

Evidence and Recommendations criteria

To formulate recommendations, the strengths and limitations of the available evidence were considered, as well as benefit versus harm and applicability to clinical practice context. Details of study methodology limitations, appropriateness of primary and secondary outcomes, and consistency of results across studies were discussed in the main text.

Tables of Evidence

The members of the GWC provided summaries of the selected articles, used to support the evidence for the different recommendations, in Tables of Evidence (ToEs). These ToEs are available online, as Supplementary Material.

The revision process and update of guidelines

The guidelines document underwent external review for critical evaluation of the content and recommendations by members of the ESVS Guidelines Steering Committee, and by other independent experts in the field. After each review round, the reviewers’ general and detailed comments were compiled into one document. The manuscript was then revised according to the reviewers’ comments and all amendments were discussed and approved by all members of the GWC. In addition, a point to point reply to the reviewers was provided. After three review and subsequent revision rounds, the final document was approved and submitted to the European Journal of Vascular and Endovascular Surgery on 10 November 2021. These guidelines will be updated in 2026, according to the ESVS policy to update all guidelines which are part of the core curriculum of the vascular surgeon every four years.

The patient perspective

The importance of patient and public involvement in clinical guideline development is widely recognised and accepted. Patient engagement improves validity, increases quality of decisions, and is encouraged by national and international groups.

To improve accessibility and interpretability for patients and the public, a plain English summary has been produced for this guideline and subjected to a lay review process. Information for patients was drafted for each subchapter which was read and amended by a vascular nurse specialist and at least one lay person or patient.

Lay summaries were evaluated by a patient focus group, consisting of eight patients in the United Kingdom National Health Service with a history of CVD (six patients with C2-C5 disease and two patients with C6 disease) and three lay members of the public without CVD. All members of the focus group had been sent the lay summaries prior to the meeting, which was held virtually because of COVID-19 restrictions. At the meeting, the background and rationale for the ESVS CVD guidelines were presented and focus group feedback was obtained for each section of the document, systematically. All members of the focus group welcomed the invitation to contribute to the process and many commented that their personal experiences of care had been very different to the treatments recommended in the guidelines. Specifically, referral for specialist venous assessment had often been very delayed, although this may be a specific reflection of the United Kingdom National Health Service.

Several patients stated that they had tried compression garments but found them difficult to wear. The group felt it important to express that where compression is recommended to patients, aids to help donning and removal of the stockings should be provided. The section describing superficial venous ablation procedures was found to be complex by the patients and lay members of the focus group and was simplified accordingly. Six of the patients in the focus group had been treated with endovenous ablation procedures. The group emphasised the importance of shared decision making and stated that they would want to discuss potential treatment options even if not locally available. Feedback from the focus group was used to amend the lay summaries.

1.2.1. The superficial and perforating veins of the lower limb

The great saphenous vein (GSV) drains into the common femoral vein (CFV) at the level of the saphenofemoral junction (SFJ). The GSV lies in its saphenous compartment, which is easily recognisable on B mode ultrasound scanning. The most important accessory saphenous vein is the anterior accessory saphenous vein (AASV), which runs almost parallel and slightly lateral to the GSV in the thigh, in its own saphenous compartment (Fig. 4). The small saphenous vein (SSV) ascends upwards on the posterior calf to join the popliteal vein (POPV) in the popliteal fossa in the majority of cases, although the level of the junction with the deep venous system may vary. Veins connecting the GSV and SSV are called “intersaphenous veins”. A particular intersaphenous vein is the Giacomini vein (Fig. 4) connecting the SSV in the popliteal fossa with the cephalad GSV. DUS has revealed the large variability of the superficial veins and therefore it is mandatory to rely on the so called “duplex anatomy” to plan any treatment.^15,16 Tributaries of the saphenous trunks and accessory veins are situated in the subcutaneous tissue with a very variable distribution and present as visible or palpable, usually tortuous VVs. Perforating veins (PVs) are variable in arrangement and distribution, connecting the deep and superficial veins, with unidirectional valves assuring flow from superficial to deep veins, except in the foot. PVs form a complex subfascial network of interconnected veins.

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Figure 4. Anatomy of the main accessory saphenous veins and Giacomini vein (intersaphenous vein connecting the small saphenous vein with the great saphenous vein). In the presence of a Giacomini vein, the saphenopopliteal junction may be present or absent.

1.2.2. The deep veins of the lower limb

The paired posterior tibial veins and the peroneal veins in the calf join to form the tibioperoneal trunk, which joins the anterior tibial veins. Large veins of the soleus and gastrocnemius muscles join these to form the POPV. This ascends in the adductor canal becoming the femoral vein (FV), which joins the deep femoral vein (DFV) to form the CFV in the groin. Above the inguinal ligament, the CFV continues as the external iliac vein (EIV) and, after receiving the internal iliac vein (IIV), continues as the common iliac vein (CIV). On the left side the CIV passes between the right common iliac artery and the vertebral column. From the confluence of the right and left CIV, the inferior vena cava (IVC) ascends alongside the right of the aorta.

1.2.3. Small veins and the microvenous circulation

Small veins of the subcutaneous and cutaneous venous network have been studied less extensively than large veins and their valves.¹⁷ Previously, the belief was that venous valves did not exist in veins and venules of < 2 mm. However, detailed studies of small veins in the skin of the lower leg showed that valves do exist even in veins with a diameter from 100 μm – 2 mm, and that these microvenous valves also can be incompetent.¹⁸ A study using retrograde resin venography in amputated lower limbs demonstrated that valvular incompetence can exist in these small veins, independently of valvular competence of the GSV. In the third generation of tributaries from the GSV the so called “boundary” valves can be seen, which are able to prevent reflux to the skin. When GSV reflux is present, incompetence of these microvalves may play a critical role in progression of skin changes.¹⁹

1.4.1. Symptoms

The symptoms of CVD are extremely variable and may cause significant morbidity to patients, negatively affecting quality of life (QoL). Symptoms increase with age and are more commonly reported in women. Patients may present with heaviness, tired legs, feeling of swelling, itching of the skin, nocturnal cramps, throbbing, burning pain, aching of the legs, which is exacerbated by prolonged standing or sitting, or venous claudication during exercise. It is sometimes difficult to attribute symptoms to a venous aetiology and call them “venous symptoms”. All clinical CEAP classes from C0_S to C6 can be associated with the same symptoms, which do not necessarily correlate with the presence or severity of venous hypertension.²⁸ CVD can be asymptomatic, even in limbs with extensive VVs and even C4 and C5 clinical CEAP class, while venous symptoms can be present without any clinical sign of CVD (C0_S). On the other hand, similar symptoms are frequently present in patients with other diseases of the lower limbs.²⁹

Symptoms of heaviness, sensation of swelling, burning, itching, and pain/aching are associated with higher C of the CEAP clinical class both in intensity and number of symptoms. Symptoms such as fatigue, cramps, and restless legs are less specific for CVD.^30,31

Venous claudication is a symptom presenting as increasing pain on exercise. It is caused by outflow obstruction at the iliofemoral and/or caval level as well as popliteal vein entrapment, leading to limited walking capacity.²⁸ In a small study in 39 patients, at a median follow up of five years after iliofemoral DVT, a standardised treadmill test (3.5 km/h, slope 10%) elicited venous claudication, necessitating interruption of walking in 15% of patients.³²

1.4.2. Signs

In CVD, clinical signs are described per limb as the “C” component of the CEAP classification, from C1 to C6 (Table 3).⁶ Other typical clinical signs, not included in the CEAP classification, are the presence of cross pubic collaterals in case of unilateral iliac vein obstruction, abdominal collaterals in case of IVC obstruction (caused by previous DVT, congenital absence/hypoplasia, or extrinsic compression) (see Chapter 5) and vulvar VVs in women with pelvic venous disorders (PeVD) (see Chapter 7).

1.4.3. Acute complications

Acute complications are uncommon in patients with CVD. The most common is SVT, which may be limited to a varicose tributary, or affect a saphenous trunk. This can be complicated by extension into the deep venous system as a concomitant DVT and, exceptionally cause pulmonary embolism (PE). In patients with CVD, DVT or a recurrent DVT may occur. In general, VVs are considered a minor risk factor for developing DVT, as discussed in the ESVS guidelines on the management of venous thrombosis.² In a population based study it was concluded that it is unclear whether the association between VVs (without SVT) and DVT is causal or a result of common risk factors.³³

Another acute complication is haemorrhage, which is commonly associated with a traumatised superficial vein or telangiectasia, but significant bleeding can also arise from an area of ulceration. The resulting blood loss may be extensive and even life threatening.³⁴

1.5.1. Clinical scoring systems

1.5.2. Patient reported outcome measures

Patient reported outcome measures (PROMs) are often considered the “gold standard” tools for evaluating success after interventions. There is a range of validated disease specific and generic PROMs available. However, they can be complex and time consuming to use and analyse, which is a limit to their applicability in clinical practice. A detailed description of all these tools is beyond the scope of the present guidelines. Commonly used disease specific QoL tools in CVD are the Aberdeen Varicose Veins Questionnaire (AVVQ) (Supplementary Table S1),³⁹ the Chronic Venous Insufficiency Questionnaire (CIVIQ) (Supplementary Table S2),⁴⁰ and the Venous Insufficiency Epidemiological and Economic Study quality of life/symptoms (VEINES-QOL/Sym) (Supplementary Table S3).⁴¹ Despite the potential advantages, use of patient reported QoL tools is uncommon outside clinical trials and health economic studies. Nevertheless, the importance of PROMs is recognised increasingly and mandated in some international venous registries.

2.3.1. Duplex ultrasound of the lower limbs

DUS of the lower extremities is the primary diagnostic test of choice in patients with CVD.^15,43,44 It provides information about venous anatomy, patency, vein wall pathology, and flow. Morphological examination of deep veins and evaluation of normal phasic flow in the CFV may be performed in the supine position. To evaluate the presence or absence of reflux, DUS is preferentially done in the upright position with the knee of the investigated leg slightly bent. Reflux must be provoked, either from above with dependency testing or a Valsalva manoeuvre, or from below, using an automatic pneumatic pressure cuff or manual compression of the thigh, calf, or foot.^15,44 The Valsalva manoeuvre is typically used to assess the SFJ. The clinical significance of measuring reflux duration is questionable other than to establish its presence beyond a cut off duration. It depends on the provocation manoeuvre used and may be difficult to quantify. The cut off values most used are 1 second for reflux in the CFV, FV and POPV and 0.5 seconds in superficial veins and PVs, although 0.35 seconds has been used as a threshold for PVs as well.^16,44,45 Other useful information on ultrasound in CVD includes the course of the reflux, the length of the refluxing trunk, and saphenous trunk diameter, which should be measured in the upright position in a vein segment without focal dilatation (for the GSV at about 15 cm from the SFJ).^46,47 A detailed methodology for performing DUS of the lower extremities has been described previously.^15,16 In addition to a written DUS report, it is important to make an accurate graphical representation of the DUS findings in the superficial and deep veins of the examined limbs, called “venous mapping”. This is an essential tool to plan and perform venous interventions.

2.3.2. Abdominal ultrasound

Whenever there is a suspicion of supra-inguinal pathology, based on clinical examination (extensive unilateral oedema, healed or active VLU, abdominal wall collaterals) or on specific DUS findings while examining the lower limbs (absence of phasic flow in the CFV, or post-thrombotic fibrosis in the deep veins), the next step is to perform an additional abdominal DUS. It should be acknowledged that DUS examination of abdominal and pelvic veins (i.e. gonadal veins and IIVs) requires appropriate expertise. If this is not available, cross sectional imaging may be preferred. In certain patients it may be technically difficult to perform abdominal DUS because of abdominal obesity or the presence of bowel gas. Abdominal DUS is preferably performed after the patient has been fasting overnight.⁵⁰ The patient is placed in supine position and the IVC and iliac veins are examined with DUS to detect potential compression or luminal obstruction and to evaluate direction of flow and velocities. The presence of collaterals, absence of phasic flow in the CFV, and flow velocity changes may indicate obstruction.^51,52 When DUS was compared with intravascular ultrasound (IVUS), a velocity ratio (maximum through obstruction velocity/maximum pre-obstruction velocity) ≥ 2.5 was found to be the best criterion for detecting significant venous outflow obstructions in iliac veins.⁵¹ When PeVD are suspected, the left renal, gonadal, peri-uterine and para-vaginal veins, and the tributaries of the IIVs are examined.⁵⁰ After venous thrombolysis and stenting, DUS is often used for patency surveillance.

2.4.1. Magnetic resonance venography

MR venography (MRV) can provide information about the venous system that is enhanced by 3-D reconstruction. Dynamic imaging information can be provided as well with regard to velocity and volume. MRV can visualise deep vein obstruction, fibrotic scarring of the vein wall and in the lumen (post-thrombotic fibrosis), as well as collaterals and VVs.⁵⁵

2.4.2. Computed tomography venography

CT venography (CTV) is generally more available than MRV and its imaging protocols receive wider acknowledgement by the medical community.⁵⁶ Obviously, CTV necessitates the use of iodinated contrast and ionising radiation, comparing unfavourably with MRV. There are two main techniques for performing lower limb CTV. Indirect CTV is performed as post-intravenous contrast enhanced CT, with imaging results largely dependent on cardiac output, size of the intravenous line, rate of injection, and degree of hydration. Direct CTV generally involves intravenous injection of contrast in the foot or directly into the FV or POPV with ascending acquisition of imaging, providing improved detail. Direct CTV may allow for increased detailed imaging of luminal pathology. However, contrast transit times are hard to predict and therefore adequate imaging of abdominal, pelvic, and peripheral veins may be cumbersome.

2.5.1. Venography

Classical ascending venography (also called phlebography) by access and contrast injection from a foot vein has no additional value over DUS to screen for deep venous obstruction and is now considered obsolete. Venography with access gained through the POPV, FV, or CFV, has previously been used to evaluate particular aspects of supra-inguinal venous obstruction. It can indirectly diagnose left CIV obstruction through the identification of a combination of collaterals and a flattened CIV (pancaking).⁵⁷ Although multiplanar venographic imaging in at least two perpendicular projections may improve its diagnostic value, it is impractical and increases radiation exposure and iodinated contrast use. Another challenge relates to the immobile, prone, or supine position of the patient, which may over- or underdiagnose CVD. Intravenous imaging of proximal venous outflow obstruction has primarily been substituted by IVUS. However, the method can still be used if other imaging techniques are inadequate or unavailable. Descending venography may also be applicable in rare cases where deep valve reconstructive surgery is being considered (see subsection 5.4).

2.5.2. Intravascular ultrasound

IVUS has become an increasingly useful investigation for deep venous pathology over the last decade. Like CTV and MRV, IVUS accurately determines cross luminal diameter and surface area of the deep veins. However, in addition, IVUS can identify subtle intraluminal changes and vein wall abnormalities that may remain obscure if other imaging techniques are used. It has been shown to be more sensitive than venography in identifying deep venous lesions, as has been shown in the VIDIO trial. In this RCT, 100 patients with C4 to C6 CEAP clinical class and suspected iliofemoral vein obstruction underwent both IVUS and multiplanar venography. IVUS proved to be more sensitive than venography in identification and quantification of iliofemoral vein obstructive lesions. Therefore, IVUS may provide an additional advantage in patient selection for venous stenting.⁵⁸ However, IVUS is an invasive modality and can be used only if the lesion of interest can be crossed with a guidewire first.

3.2.1. Elastic compression stockings, adjustable compression garments, and inelastic bandages

3.2.2. Other compression methods

3.3.1. Ruscus extracts

A systematic review on Ruscus extracts has identified 10 double blind placebo controlled RCTs involving 719 patients with unilateral or bilateral CVD (CEAP clinical class of affected limbs ranging between C2 and C5).¹⁰⁷ On quantitative analysis, Ruscus extracts significantly improved several leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, paresthesia, global symptoms, and clinical findings such as ankle circumference and leg/foot volume.

3.3.2. Micronised purified flavonoid fraction

A systematic review on micronised purified flavonoid fraction (MPFF) identified seven double blind placebo controlled RCTs involving 1 692 patients.¹⁰⁸ On quantitative analysis, MPFF improved several leg symptoms (Table 8) functional discomfort, QoL, and ankle circumference.

3.3.3. Calcium dobesilate

Calcium dobesilate is a synthetic VAD, which had been evaluated in 10 RCTs up to 2004 involving 778 patients included in a meta-analysis.¹⁰⁹ It significantly reduced a number of leg symptoms (Table 8) and discomfort, while lower limb oedema was improved and the investigators’ opinions of symptom improvement were positive, albeit with some heterogeneity. Subgroup analysis showed greater improvements in pain, heaviness, paresthesia, and leg oedema in the group of patients with severe symptoms and signs than in those with milder ones. Four more recent double blind placebo controlled RCTs involving 1 165 patients with CVD also showed improvement of symptoms and objective measures of oedema, again with some heterogeneity.110, 111, 112, 113

3.3.4. Horse chestnut extract

A Cochrane review on horse chestnut extract of 17 RCTs involving 1 593 patients showed that this VAD was effective (Table 8).¹¹⁴

3.3.5. Hydroxyethylrutosides

A systematic review and meta-analysis of the efficacy of hydroxyethylrutosides for treating symptoms and signs of CVD reported on 15 trials involving 1 643 participants.¹¹⁵ It showed that hydroxyethylrutosides significantly reduced venous symptoms (Table 8).

3.3.6. Red vine leaf extract

The effect of red vine leaf extract has been evaluated in two RCTs involving 260 and 248 patients, respectively.^116,117 Red vine leaf extract reduced CVD related symptoms and lower limb oedema substantially more than placebo, although only pain was reduced in both RCTs (Table 8). A third cross over double blind RCT assessed objective measures of oedema and patient reported global assessment of efficacy, both in favour of red vine leaf extract.¹¹⁸

3.3.7. Sulodexide

Sulodexide was evaluated by a 2020 meta-analysis, which included 13 studies on 1 901 participants.¹¹⁹ Sulodexide decreased the intensity of pain, cramps, heaviness, feeling of swelling (Table 8), and total symptom score, and also reduced inflammatory mediators in patients with CVD.

3.3.8. Clinical applicability

Unlike the Cochrane review presented above, which pooled the results of all VADs,¹⁰⁵ the present guidelines used published individual meta-analyses; some of the latter studies used the GRADE approach like Cochrane reviews to quantify the certainty of evidence, a methodology not used by the ESC and the ESVS guidelines, so that some of their findings on certainty of evidence are not applicable herein. Furthermore, based on results of the Cochrane review, it is evident that VADs do help patient symptoms, although MPFF and Ruscus extract VADs were not included there. Given the low cost of VADs and their rare side effects that are usually not severe, VADs at least should be considered for the treatment of symptoms and oedema related to CVD. The GWC has decided to provide a single generic recommendation on VADs, as opposed to individual ones, on the understanding that these agents represent a heterogeneous group. The same class of recommendation as cited in the 2015 edition has been retained, taking into account the latest meta-analyses for MPFF and Ruscus extract.^107,108

4.1.1. Indications for treatment

In CVD patients with superficial venous incompetence, management strategies mainly depend on clinical presentation (history, symptoms, signs) and detailed individual DUS findings, which are all mandatory for proper decision making. In addition, the negative impact of CVD on QoL should be considered. Many studies have shown the beneficial effect of intervention on venous symptoms, as well as on disease specific and generic QoL, not only in CVD patients presenting with skin changes (CEAP clinical class C4 – C6), but also in those with VVs only.^120,121 In the REACTIV trial, a group of 246 patients with symptomatic uncomplicated VVs (CEAP clinical class C2 – C3) were randomised between surgical intervention and conservative treatment, consisting of lifestyle advice and ECS. In the first two years after treatment there was a significant QoL benefit for surgery, based on the EQ-5D score. Significant benefits were also seen in symptomatic and anatomical measures.¹²² Further analysis showed the cost effectiveness of surgery versus ECS in these patients with uncomplicated VVs.¹²³ A more recent investigation into the cost effectiveness of interventional treatment for VVs in the UK National Health Service similarly concluded that interventional treatment for VVs is cost effective, with endovenous thermal ablation (EVTA) being the most cost effective for those patients for whom it is suitable.¹²⁴ Another review suggested that surgery and the minimally invasive techniques are similar in terms of efficacy or safety, so the relative cost of the treatments becomes one of the deciding factors.¹²⁵ However, the investigators noted that high quality RCT evidence is required. It is therefore obvious that the above findings may not be applicable to all patients worldwide, as cost effectiveness largely depends on the local resources and healthcare situation.

Although the natural history of the disease has not been extensively investigated in CVD patients, long term follow up data of the Edinburgh Vein Study (after 13 years) clearly revealed disease progression, with one third of patients with isolated VVs at baseline developing skin changes (see subsection 1.1).¹¹ Based on all these findings, interventional treatment for patients with symptomatic uncomplicated VVs resulting from superficial venous incompetence (CEAP clinical class C2_S) is justified.

For CVD patients presenting with oedema (CEAP clinical class C3), without clinically evident VVs, it is less clear whether they require treatment for superficial venous incompetence, as oedema, certainly if bilateral, may be multifactorial, with several coexisting causes of oedema, not related to venous disease and hence non-responsive to venous intervention. Therefore, other non-venous causes of oedema should be considered before planning interventional treatment of venous incompetence. On the other hand, patients presenting with symptomatic VVs and oedema (CEAP clinical Class C2,3_S) may be more likely to benefit from superficial venous intervention, with reduction of oedema after the procedure. In general, unilateral limb swelling is considered a better predictor for a favourable response than bilateral oedema.¹²⁶

For CVD patients presenting with skin changes (CEAP clinical class C4 – C6), there is consensus that treatment of superficial venous incompetence is indicated and constitutes an appropriate use of healthcare resources.¹²⁶ Whereas the beneficial effect of reflux ablation on ulcer healing has been clearly proven (see Chapter 6), only limited (empirical) data are available concerning the effect of superficial venous intervention on other skin changes.

For patients with reticular veins and/or telangiectasias (CEAP clinical class C1) and/or VVs with mainly cosmetic concerns, intervention is not mandated. Before intervention is performed, thorough information should be given about the low risk of serious complications of CVD, and the risk profiles and costs of different treatments, as part of a shared decision making process.

Whether treatment is “required” and which management strategy to be preferred will depend on individual patient characteristics as well. For example, patients with a high body mass index (BMI), extensive comorbidities, on anticoagulant treatment, etc., may need special attention when planning treatment.¹²⁷ These special patient characteristics are further addressed in subsection 8.2.

In summary, clinical assessment, DUS findings, and individual patient related factors remain the basis for individualised treatment. When defining the treatment strategy for patients with CVD, physicians should also take into account patient preference, as well as the expected impact on QoL, the estimated risk of deterioration of CVD and local healthcare resources, which determine the available interventional options.¹²⁷ The risks specific to each modality should also be discussed with the patient prior to any intervention.¹²⁸

4.1.2. Setting

Historically, superficial venous incompetence has been treated by open surgical repair, typically performed in an operating room, under general or regional anaesthesia. Endovenous intervention, with or without phlebectomies, is now widely acknowledged as the established standard of care and ideally should be performed in the ambulatory setting, in a properly equipped treatment room.¹²⁹ Observational data suggest that this practice is safe and effective, offering a reduction in procedural cost.^130,131 Indeed, ambulatory intervention, using tumescent anaesthesia, permits a comprehensive treatment strategy addressing both saphenous trunk and tributary incompetence. In addition, early ambulation may reduce thromboembolic risk. Therefore, in those with straightforward saphenous anatomy according to DUS, ambulatory endovenous ablation with adjunctive phlebectomies (where applicable), is advocated in the initial management of superficial venous incompetence.

4.1.3. Anaesthesia

Tumescent anaesthesia, performed under ultrasound guidance, is the preferred anaesthesia for EVTA and has also been used in recent RCTs, comparing EVTA with open GSV surgery.132, 133, 134 It allows early return to normal function and significant improvements in QoL.¹³³ Tumescence reduces pain, induces venous compression and spasm leading to greater effectiveness, and acts as a heat sink to protect surrounding structures.

A standardised tumescence composition has been described,¹³⁵ consisting of 445 mL crystalloid, 50 mL 1% lidocaine plus 1:100 000 adrenaline and 5 mL 8.4% sodium bicarbonate, with the latter offering a reduction in the burning sensation associated with injection.¹³⁶ Lidocaine doses up to 15 mg/kg, as used in tumescent anaesthesia solutions, have been associated with a minimal side effect profile, with toxicity seen in 36% of those dosed at 35 mg/kg.¹³⁷ Recent RCT data have identified reduced pain when the pH of acidic lidocaine solutions is neutralised by the addition of sodium bicarbonate, to create buffered solutions.¹³⁸ Moreover, the addition of adrenaline prolongs the anaesthetic effect and provides a vasoconstrictive effect. Finally, the practitioner should be aware that a range of formulations might not comply with the local regulations of some countries.¹³⁹ In general, additives should be limited to what is useful and relevant for venous treatments.

General and regional anaesthesia are now largely reserved for those undergoing open surgical interventions, those with very extensive tributary or PV disease and those requiring concomitant deep venous intervention. Nonetheless, contemporary open surgery, using tumescent anaesthesia, has been described increasingly.132, 133, 134

4.1.4. Cannulation and other technical considerations

For EVTA and all non-thermal ablation techniques, cannulation of incompetent saphenous trunks is performed under ultrasound guidance in a standardised way – with the probe in either longitudinal or transverse orientation,¹⁴⁰ using a 4 to 7 Fr introducer kit, depending on the device used. Cannulation prior to the administration of tumescence, can be facilitated using a reverse Trendelenburg position and a small volume of local lidocaine. Special considerations include intraluminal obstacles, such as fibrotic scars of previous SVT or thickened valves, encountered while navigating the laser fibre or catheter in truncal veins. These may be overcome using additional manoeuvres and, if needed, multilevel catheter access and over the wire ablation systems.¹⁴¹ For thermal ablation procedures, access is usually gained to the most distal incompetent segment, if located above midcalf.¹⁴² The access point can be more distal for non-thermal ablation, as the risk of neurological injury is almost absent with these techniques. Access to the saphenous trunk can sometimes be facilitated by cannulating a superficial tributary.

Sclerotherapy can be performed through a needle, a cannula, a butterfly needle, or a long catheter. Several injection methods can be applied, without any evidence of superiority of one over the other.¹⁴³ Details are further discussed in subsection 4.2.2.2.

4.1.5. Compression after treatment

Compression therapy following superficial venous intervention remains a controversial issue, particularly with regard to the indications for and benefits of therapy. Nevertheless, it is still used by the vast majority of surgeons.¹⁴⁴

The rationale for compression following venous treatments is to establish luminal compression of the treated vein or of the area where veins have been removed (by stripping or phlebectomy), to prevent or minimise inflammation, pain, bruising, bleeding, haematoma, and superficial or deep vein thrombosis.^145,146 However, to compress the GSV effectively at thigh level, compression of > 40 mmHg is necessary in the standing position.¹⁴⁷ This is nearly impossible to achieve with ECS alone, but it is possible when the stocking is applied on top of an eccentric compression pad, placed directly over the ablated or surgically removed vein. In a small RCT, applying a thigh length ECS with 35 mmHg ankle pressure, placed on top of eccentric pads on the treatment area, was more effective in reducing post-procedural side effects than a 23 mmHg ECS.¹⁴⁸

There is conflicting evidence from several RCTs comparing compression with no compression after both EVTA and ultrasound guided foam sclerotherapy (UGFS) of saphenous trunks.149, 150, 151, 152 Additionally, the interpretation and comparison of trials is difficult because of heterogeneity in modality and the degree of compression applied, variations in the duration of compression, and incomplete reporting of compression therapy compliance. In the largest trial, randomising 400 patients, undergoing endovenous laser ablation (EVLA) of the GSV, between ECS exerting 23–32 mmHg and no compression, early results were beneficial for ECS. In the first week after EVLA, patients in the ECS group experienced less pain (p < .001) and oedema (p = .010), but by two weeks these variables were similar between the groups.¹⁵⁰

Concomitant treatment of varicose tributaries may be taken into account when deciding whether or not to offer post-procedure compression. According to the COMETA trial, wearing compression stockings after EVTA was beneficial, with better pain scores during the first week, and especially for those having concurrent phlebectomies,¹⁵¹ while another study, where radiofrequency ablation (RFA) and concomitant UGFS of tributaries was performed, reported the opposite results.¹⁵³ Based on clinical experience, eccentric compression at the sites of tributary treatment may be useful, even if its use has not been specifically investigated.

Duration of post-procedure compression is also controversial and is mainly left to the clinical judgement of the treating physician.¹⁵⁴ Based on a meta-analysis including five RCTs (775 patients) examining compression durations ranging from 24 hours to two weeks, compression for at least one week was recommended by the authors following EVTA.¹⁵⁵ This confirmed the findings of a previous meta-analysis, where compression for 3 – 10 days showed the same benefit as compression for a longer duration.¹⁴⁶

4.1.6. Thromboprophylaxis

Significant variations in thromboprophylaxis practice exist with sparse supportive data. While many clinicians administer a single dose of prophylactic low molecular weight heparin (LMWH) to all patients peri-operatively, this practice is not supported by the evidence to date. One RCT evaluating 2 196 patients undergoing open GSV surgery followed by no prophylaxis, subcutaneous unfractionated heparin (UFH) or LMWH (either 6 000 international units [IU] once a day or 4 000 IU twice daily) for three days post-operatively reported lower rates of ultrasound detected DVT within 30 days of intervention in those receiving prophylaxis.¹⁵⁶ The reported rates of DVT were 5.17% in the no prophylaxis group compared with 0.56% in the UFH group and 0.35% (6 000 IU once daily) or 0.36% (4 000 IU twice daily) in the LMWH cohort. The majority of DVTs described were located in the POPV, with more proximal DVTs identified only in the group receiving no prophylaxis. Notably, haemorrhagic complications were higher (0.75%) in the UFH group alone. The benefit of thromboprophylaxis after HLS was not seen in a smaller RCT assessing moderate-risk patients randomised to compression and early ambulation with or without 10 days of LMWH (bemiparin 2 500 IU or 3 500 IU once a day).¹⁵⁷ High risk patients (e.g., previous DVT, family history of venous thromboembolism [VTE], known thrombophilia, obesity, neoplasia, concomitant interventions, elevated pre-operative inflammatory markers [C reactive protein and D dimer]) benefit from prophylaxis during the 7–10 post-operative days, based on individual risk assessment.158, 159, 160 In contrast there is little evidence to support prophylaxis in the low risk cohort undergoing endovenous ablation. Routine thromboprophylaxis may expose this cohort to potentially unnecessary side effects. In a UK and Ireland survey, vascular surgeons agreed that thromboprophylaxis with LMWH should be given to patients with increased VTE risk for one to two weeks rather than a single dose.¹⁶¹ In view of the paucity of available data, no specific dose regimens can be recommended for LMWH prophylaxis in superficial vein treatment. Direct oral anticoagulants (DOACs) are increasingly prescribed for peri-procedural thromboprophylaxis given their convenience compared with LMWH.¹⁶² Early retrospective evidence suggests they are effective and safe.^162,163 However, comparative data with LMWH are yet to be established. For all patients early ambulation and compression hosiery may further reduce thrombotic risk.

4.1.7. Surveillance

After initial “one stop” treatment (such as endovenous ablation or surgery) it is common practice to perform DUS surveillance of the treated vein(s) one to four weeks after treatment, to check whether the intervention has achieved the intended immediate goal and to check for absence of post-operative DVT.¹⁶ For patients undergoing sequential treatments, such as staged sclerotherapy, or other combined treatments in different steps, interval DUS is performed before the subsequent treatment stage.¹⁶⁴ For most patients, repeat DUS assessment is required only for suspected clinical recurrence.

4.1.8. Safety and environmental sustainability issues

Venous interventions are well tolerated and undertaken increasingly often in the ambulatory setting. Indeed, endovenous strategies now offer effective treatment even in the frail and elderly.¹⁶⁵ Both ablative and open techniques are largely associated with a limited side effect profile, but are not completely without risk.¹²⁸ These risks are further described in subsection 4.2. As such, careful pre-operative risk assessment, to aid stratification, should be undertaken on an individual basis to determine optimal management strategies.

Transition of care from operating rooms to outpatient based environments has the potential to further reduce the resource demand associated with venous intervention. Furthermore, environmental sustainability could potentially be enhanced by described experimental reprocessed multi-use catheters.¹⁶⁶

4.2.1. Thermal ablation

4.2.2. Non-thermal ablation

4.2.3. High ligation and stripping

Venous reflux elimination through HLS of the GSV or SSV with additional phlebectomies has been the standard treatment for VVs for many years and may still be a valuable option. Nowadays, similar to EVTA, HLS can be performed under local or tumescent anaesthesia with ultrasound guidance, a strategy that has been followed in several RCTs comparing EVTA with HLS.^{132,134,175,235} This means general anaesthesia is not mandatory for “modern” HLS.

As already discussed in subsection 4.2.1.2, long term (five year) results of EVTA and HLS are not different with respect to clinical VV recurrence or recurrent reflux detected by DUS, although the site of recurrence may be different.^{134,177,200,202,203} In addition, a meta-analysis looked at pooled long term outcome data (five years) of two RCTs and 10 follow up studies of RCTs on treatment of GSV incompetence. Recurrent reflux rates at the SFJ were statistically significantly lower after HLS than after EVLA (12%, 95% CI 7 – 20% vs. 22%, 95% CI 14 – 32%; p = .038). The r-VCSS scores were also pooled for HLS and EVLA and showed similar improvements.²⁰¹

When comparing complications after HLS with those after EVLA, bleeding and haematoma (4.8% vs. 1.3%), wound infection (1.9% vs. 0.3%), and paraesthesia (11.3% vs. 6.7%) were more frequent after HLS.²³⁶

4.3.1. Phlebectomies

The technique for ambulatory phlebectomy (AP) involves multiple small (2 – 3 mm) longitudinal incisions overlying pre-operatively marked VVs. Incisions are performed under local anaesthesia. The targeted VVs are removed with specially designed phlebectomy hooks and fine tipped mosquito clamps. Tributary intervention is typically performed as an adjunct to truncal ablation for associated large incompetent tributaries (> 5 mm diameter) or in isolation where truncal competence is confirmed on DUS. Also, it can be part of specific treatment strategies with preservation of the saphenous trunk (see subsection 4.6.7). In those undergoing saphenous ablation the need for additional AP should always be discussed with the patient to facilitate shared decision making.

With the development of EVTA, most interventions are performed using tumescent anaesthesia. Tumescent anaesthesia also is routinely used for AP, which may be performed during the same endovenous ablation procedure. A small RCT (50 patients), comparing AP with no tributary intervention as an adjunct to EVLA using tumescence, identified no difference in peri-procedural complication rates and pain between cohorts.²³⁷ Whether to perform concomitant or delayed phlebectomies, in the context of EVTA, will be discussed further in subsection 4.6.4.

Complications of APs are generally infrequent and mild: blisters (5.4%), hyperpigmentation (4.6%), matting (3.6%), SVT (2.8%), DVT (0.02%), dysaesthesia (0.4%), lymphocoele (0.2%), post-operative haemorrhage (0.1%), large haematoma (0.1%), and infection (0.07%).²³⁸

4.3.2. Sclerotherapy of tributaries

Sclerotherapy offers a minimally invasive alternative to AP. It is used frequently as an adjunct to endovenous truncal ablation or to treat residual varicose tributaries and non-saphenous VVs as it is well tolerated without the need for anaesthesia and may be performed repeatedly in the ambulatory setting. In the treatment of incompetent tributaries, foam based sclerotherapy is used widely as it is more effective and allows a reduction in the amount of injected sclerosant.²¹⁹ Liquid sclerotherapy is reserved largely for treatment of reticular veins and telangiectasias (see subsection 4.5.1).¹⁴³ The concentration of the sclerosant used depends on the size of the treated vein. A systematic review found no significant difference in effectiveness and symptom improvement of any commonly used sclerosant.²³⁹ Cannulation of non-clinically visible VVs always should be performed under ultrasound guidance to limit complications. There is no evidence based limit to the maximum volume of foam per session, although current consensus suggests a maximum use of 10 – 20 mL of foam per treatment.^143,240 This corresponds with the previously proposed limit of 16 mL, to comply with European regulations (see subsection 4.2.2.2).

In foam based strategies, larger VVs should be targeted initially to encourage wider foam dispersal with subsequent interventions reserved for residual tributaries, reticular veins, and telangiectasias. Successful ablation of tributary disease often requires a staged approach including a number of UGFS sessions.²⁴¹ This treatment strategy is characterised by intermittent ambulatory clinical and DUS review, with subsequent UGFS of residual refluxing veins in a stepwise fashion.

The efficacy of sclerotherapy in treating tributaries and non-saphenous VVs has been described in the literature. One RCT showed statistically significantly higher patient satisfaction after non-saphenous vein sclerotherapy than after placebo (p < .001), with 85.9% of patients satisfied or very satisfied with the treatment.²⁴² Another RCT found that in those with minor below knee VVs, sclerotherapy statistically significantly reduced the proportion of people reporting aching and cosmetic concerns compared with conservative treatment after one year (p < .050).²⁴³ Greater symptomatic improvement has been demonstrated after liquid sclerotherapy for isolated tributary disease compared with compression hosiery, without the need for long term compression (p < .001).²⁴⁴

In a RCT comparing sclerotherapy with AP for below knee VVs, sclerotherapy resulted in a statistically significant improvement in symptoms (p < .050), which was comparable with AP.²⁴³ At one year follow up, there were no visible VVs in 76% of patients after surgery and 39% after sclerotherapy (p < .050). Despite this, no statistically significant difference in patient satisfaction was observed.²⁴³ Another RCT, which compared liquid sclerotherapy with AP in the management of isolated tributary incompetence (n = 98), identified statistically significantly higher rates of recurrent disease in those undergoing sclerotherapy at one (25% vs. 2.1%, p < .001) and two years (37.5% vs. 2.1%, p < .001). Rates of phlebitis were comparable in each group; however, AP was statistically significantly associated with both blister and scar formation.²⁴⁵ It should be noted that the treatment protocol for sclerotherapy of tributaries, used in these trials, was not optimal, as liquid sclerosant was used.

In patients with CVD treated with endovenous ablation of an incompetent saphenous trunk, additional UGFS may be useful for treating small varicose tributaries (< 5 mm). However, the timing of such adjunctive treatment, either concomitant or delayed, remains unclear (see subsection 4.6.4).

Whether to opt for AP or UGFS for varicose tributaries depends largely on the physician’s experience and preference in view of the patient’s expectations. According to a worldwide survey about management strategies for patients with VVs, in which 211 physicians from 36 different countries participated, APs were as frequently used as UGFS for refluxing tributaries. However, there was a preference for phlebectomies in cases where tributaries had a large diameter, a superficial course, or where they were visible, and a preference for UGFS in other cases (p < .001).²⁴⁶ In patients presenting with skin changes, in particular lipodermatosclerosis (CEAP clinical class C4b), adjacent phlebectomies may be complicated by delayed wound healing. In these cases, UGFS is a valid alternative option.

4.3.3. Other techniques for varicose tributary treatment

Transilluminated powered phlebectomy provides an alternative treatment for varicose tributaries, in particular in those limbs with extensive VVs offering the benefit of fewer incisions and shorter procedural times.²⁴⁸ However higher rates of ecchymosis (39% vs. 25%, p < .001) and pain with inferior early QoL have been reported in a RCT comparing transilluminated powered phlebectomy with AP.²⁴⁹ A learning curve should certainly be taken into account.²⁵⁰

Endovenous laser treatment of incompetent tributaries offers a further therapeutic alternative, mainly applicable for large varicose tributaries.²⁵¹ Only limited retrospective data are available so far, suggesting that EVLA of tributaries may be associated with higher rates of tributary re-intervention (21.6%, vs. 4.9%, p < .010) when compared with adjunctive UGFS of tributaries.²⁵²

4.4.1. Perforating vein ligation

Surgical ligation of incompetent PVs through a short incision has been studied prospectively in 145 limbs where 850 incompetent PVs were identified and ligated. The closure rate was 94.3%. Sclerotherapy was used to complete closure. After three years, 67.8% of the ligated PVs remained obliterated.²⁵⁵

In the absence of endovenous options, open PV ligation is feasible in selected patients, particularly in cases with healthy overlying skin, such as recurrent VVs from a popliteal fossa PV.²⁵⁶ In preparation for open intervention all PV positions should be marked with ultrasound routinely. However, despite pre-operative marking, the anatomy may be challenging with complex subfascial and subcutaneous branching systems, and thus predispose to recurrence.²⁵⁵ An alternative approach is to perform a phlebectomy of tortuous subcutaneous PV branches through stab incisions. To date exact procedural success rates are unknown given a paucity of data.

4.4.2. Perforating vein ablation

PV ablation has been reported widely, including EVLA, RFA, MOCA, CAC, and ultrasound guided injections with sclerosing agents, liquid, or foam.^190,253,257, 258, 259, 260, 261 Direct cannulation of PVs is often difficult because of tortuosity of the vein and the condition of the overlying diseased or ulcerated skin. Adjacent VVs may be traversed to gain indirect access from sites of healthy skin. While short introducers provide adequate access for regular endovenous catheters, cannulation may be further facilitated by small diameter catheters and shorter heating elements (e.g., stylet, for RFA). Increasingly, specific catheters dedicated to PV intervention are available, providing a means of direct PV puncture.

The closure rate for thermal techniques such as RFA and EVLA is lower for PVs (60% – 80%) than for truncal veins (> 90% for EVLA),¹⁷³ in the available retrospective studies to date.^253,258,262 As a proportion of ablated PVs recanalise with time, routine early DUS surveillance and re-intervention is advocated, particularly in patients with VLU. Complication rates are generally low, comparable with ablation in other venous segments.

With regard to non-thermal techniques, MOCA for PVs is reported with low morbidity but closure rates are yet to be established definitively.²⁵⁹ Conversely, CAC with a catheter or direct percutaneous injection, has been reported with almost 100% closure rates at six months, although some thrombotic extensions into the deep system, phlebitis like reactions, and pain were reported in these patients.²⁶⁰

In clinical practice, the most commonly used treatment of incompetent PVs is UGFS, as it is cheap, easy to use in an outpatient setting, and requires no local anaesthesia.²⁶³ At approximately 50%, occlusion rates are lower than for RFA or EVLA, but UGFS can be repeated at follow up if needed or, in the event of failure, the PVs can be treated with another endovenous method. Complications are minimal considering its widespread use. Local calf vein DVT has been reported after 3% of 189 injections in a group of 62 patients with active VLU and a history of DVT in one third of these patients.²⁶³ There are some rare cases of inadvertent intra-arterial injection with sclerosing agent reported, causing distal ischaemia, and even requiring subsequent amputation. To avoid this, careful ultrasound guidance is of the utmost importance. Cannulation can be performed through a connecting VV, thereby avoiding the small artery adjacent to the PV.

To date there are no randomised studies comparing the reported endovenous methods for PV ablation. However tortuous PVs of smaller diameter are likely to be more suitable for sclerotherapy than larger, straighter PVs where the sclerosing agent will be washed out rapidly.

4.4.3. Other techniques

Subfascial endoscopic perforator surgery (SEPS) is a minimally invasive alternative to open PV ligation. It requires endoscopic equipment, general or regional anaesthesia, and a bloodless field. PVs are divided subfascially with diathermy or clips. The closure rate reported is higher than that of endovenous methods but there is no study providing a direct comparison between SEPS and endovenous ablation.²⁶⁴ Minor complications such as haematoma, pain, and minor nerve injury are reported in 30% – 40%, but serious adverse events are rare.

4.5.1. Sclerotherapy

Sclerotherapy is the gold standard for treating reticular veins and telangiectasias. There are two major categories of sclerosing agents used to treat patients with C1 disease, with different mechanisms of action on endothelial cells: detergents (POL, STS) or osmotics (hypertonic saline, hypertonic glucose). The effectiveness of sclerotherapy in the treatment of reticular veins and telangiectasias has been amply described in the literature, with a reported treatment success rate of 95% after POL and 91% after STS.²⁶⁶ Another RCT showed statistically significantly higher patient and investigator satisfaction after sclerotherapy with POL than after placebo (p < .001), with the percentage of patients and investigators satisfied or very satisfied ranging between 86% and 90%.²⁴² Regarding the use of foam or liquid sclerotherapy in the treatment of C1 disease, a systematic review found no evidence for superior efficacy of one form over the other, although visual disturbances seemed to be more common with foam than with liquid.²¹⁹

Analysing the difference between sclerosants, a Cochrane review found no evidence suggesting superior efficacy or increased patient satisfaction with any sclerosant.²⁶⁷ However, one RCT showed greater patient satisfaction after sclerotherapy of reticular veins and telangiectasias with POL than with STS at week 12 (88% vs. 64%, p < .001) and week 26 (84% vs. 63%, p < .001).²⁶⁶ Another RCT has also proven the greater efficacy of POL than 20% hypertonic saline solution in treatment of reticular veins > 1 mm. Good and very good results were achieved in 86% versus 67% of patients treated with POL versus HS, respectively (RR = 2.70; p = .003).²⁶⁸ Another RCT showed that a combination of 0.2% POL diluted in 70% hypertonic glucose was statistically significantly more effective than 75% hypertonic glucose alone (p < .001) in treatment of both reticular veins and telangiectasias, with no statistical difference in complications.^269,270

Comparing sclerotherapy with transcutaneous laser (TCL), sclerotherapy has been shown to be as effective as 1064 nm Nd:YAG TCL, especially in treatment of reticular veins > 1 mm, but markedly less painful.^271,272 One RCT demonstrated statistically significant lower efficacy of sclerotherapy with POL compared with 1064 nm Nd:YAG in the treatment of telangiectasias < 1 mm (95% vs. 53%; p < .001),²⁶⁸ whereas two other trials did not confirm these results and found no statistically significant difference in disappearance of veins with a diameter of 0.2 – 2.9 mm and no difference in patient satisfaction between sclerotherapy and Nd:YAG.^271,272

Sclerotherapy related adverse events have been described in detail in subsection 4.2.2.2. The majority of adverse events after sclerotherapy of reticular veins and telangiectasias are mild and the most frequent are transient hyperpigmentation, neovascularisation, and injection site scar.^242,266

4.5.2. Transcutaneous lasers and intense pulse light sources

TLC uses selective photothermolysis, to obliterate blood vessels while sparing surrounding tissues. The technique is based on proper energy delivery by selecting the wavelength, the pulse duration and providing sufficient radiant exposure to cause irreversible damage to the target structure.²⁷³

Laser light is selectively absorbed by oxyhaemoglobin and converted to thermal energy, leading to heating of the telangiectatic or reticular veins, coagulation, and vessel destruction.

Standard vascular lasers include pulsed dye lasers (PDL) (585 and 595 nm), potassium titanyl phosphate (KTP) lasers (532 nm), alexandrite lasers (755 nm), diode lasers (800 – 900 nm), and Nd:YAG lasers (1 064 nm). New developments include the use of non-uniform pulse sequences, dual wavelength modalities, and microsecond Nd: YAG lasers.²⁷⁴

When considering laser treatment for reticular veins or telangiectasias, the choice of the appropriate laser primarily depends on the size of the target vessel. Telangiectasias are usually safely and more effectively treated with shorter wavelength (< 600 nm) lasers (KTP and PDL), although the 1064 nm Nd:YAG laser also proved to be effective to treat these veins.^268,274, 275, 276 For reticular veins the use of a laser modality operating at a longer wavelength (Nd:YAG) is efficacious.^274,275 The Nd:YAG laser has been shown to be similarly effective to sclerotherapy in comparative studies, with similar patient satisfaction,^268,271,272 but it is associated with more pain, and therefore it is more suitable for specific indications, such as needle phobia, sclerosant allergy, sclerotherapy failure, and presence of small veins with telangiectatic matting. Topical anaesthetics provide safe and highly effective local anaesthesia for lower limb vein TCL therapy.²⁷⁷

An alternative treatment for larger reticular veins may consist of using alexandrite or diode lasers, although their efficacy appeared to be inferior to Nd:YAG.²⁷⁴

Intense pulsed light lasers should not be used as first line treatment because there is a relatively high risk of damaging non-vascular structures because of simultaneous delivery of multiple light wavelengths (500 – 1 200 nm).²⁷⁴

Cooling has become an integral part of laser treatments to minimise epidermal damage without reducing the effect on the target vessel. Cooling can be achieved by using a cryogen spray, cold sapphire contact handpieces or pre-cooled air, blown on the skin surface.^273,274

4.5.3. Hybrid techniques

Recent technical modifications have been reported to improve substantially the effectiveness of TCL.

Indocyanine green injected shortly before the diode laser therapy has been shown to be superior to PDL diode laser therapy alone and 1 064 nm Nd:YAG laser, but the treatment is markedly more painful than Nd:YAG laser. Therefore, a longer observation of the treated patients is needed.^278,279

The combined treatment of 1 064 nm Nd:YAG long pulse laser after foam sclerotherapy with POL has proven to be more effective than sclerotherapy alone at three months, two and three years after treatment.²⁸⁰

Cryolaser and cryosclerotherapy guided by augmented reality (CLaCS) is a new option for treating telangiectasias, reticular and feeder veins with promising results, although more studies are required for its validation.²⁸¹

4.6.1. Great saphenous vein incompetence

In those who meet the criteria for intervention (see subsection 4.1.1) strategies for treating GSV incompetence and its tributaries should be amply discussed with the patient, as part of a shared decision making process. For GSV treatment, the choice of treatment will be guided further by the respective, specific recommendations for use of each interventional modality (see subsections 4.2 and 4.3). Table 10 provides a brief illustrative summary of techniques available for treating incompetent saphenous trunks. While efficacy across several modalities (EVTA, HLS, CAC) for treating GSV incompetence is similar, EVTA has been widely advocated as the first line of care because of its excellent long term results and its cost effectiveness.¹²⁴ The decision making process and available options for treating GSV incompetence and its tributaries is further summarised in Fig. 7.

Table 10. Illustrative summary of techniques available for treating saphenous trunk incompetence

Technique	Published follow up	Reflux abolition	Quality of life improvement	Tumescence needed	Risk of nerve injury below mid-calf∗
EVTA	≥ 5 y	+++	+++	Yes	Yes
HLS	≥ 5 y	+++	+++	Yes†	Yes
CAC	3–5 y	+++	+++	No	No
UGFS	≥ 5 y	+/++‡	++/+++‡	No	No
CDFS	1 y	++	++	Yes/no	No
MOCA	3 y	++	+++	No	No

EVTA = endovenous thermal ablation; HLS = high ligation and stripping; CAC = cyanoacrylate adhesive closure; UGFS = ultrasound guided foam sclerotherapy; CDFS = catheter directed foam sclerotherapy; MOCA = mechanochemical ablation. +++ = very good effect; ++ = good effect; + = some effect (see details in subsection 4.1 – 4.3).

∗

For other complications: see details in subsections 4.1 – 4.3.

†

Or alternative anaesthesia technique.

‡

Truncal diameter < 6 mm.

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Figure 7. Interventional treatment options for patients with symptomatic great saphenous vein (GSV) incompetence. Alternative strategies, with preservation of the GSV trunk (CHIVA, ASVAL), have not been included in this flowchart. ∗Ultrasound-guided foam sclerotherapy (UGFS) only if GSV diameter is <6 mm. EVTA = endovenous thermal ablation; HLS = high ligation/stripping; CAC = cyanoacrylate closure; MOCA = mechanochemical ablation; CDFS = catheter-directed foam sclerotherapy; UGFS = ultrasound-guided foam sclerotherapy; CHIVA = ambulatory conservative haemodynamic treatment of venous incompetence in outpatients; ASVAL = ambulatory selective varices ablation under local anaesthesia.

Modern HLS, performed after detailed DUS mapping and under local or tumescent anaesthesia where possible, remains a good option with similar five year results to EVTA. Although endovenous thermal and non-thermal ablation have largely replaced open surgery in many countries, HLS can still be applied whenever equipment for endovenous ablation or expertise is not available.^127,246

The potential use of non-thermal non-tumescent techniques, such as CAC and MOCA, will depend largely on the patient’s preference, local availability of the equipment, and experience of the treating physician. Non-thermal ablation may offer lower rates of procedural pain and ecchymosis than EVTA.²⁸⁴ In addition, it may be applicable more easily than EVTA below midcalf, as no tumescence is needed. When a non-thermal technique is preferred, CAC should be the first choice as it has similar efficacy to EVTA, followed by MOCA, CDFS, or UGFS. However, as CAC is more expensive in most countries, this affects its implementation.²⁸⁵ MOCA is a reasonable alternative for patients preferring non-thermal non-tumescent treatment, even if the occlusion rate at three years was inferior to that of EVTA.²³² Another validated technique is CDFS, often applied with perivenous tumescent solution, to reduce the vein diameter during treatment. Finally, although the occlusion rate is lower, UGFS remains the most frequently performed non-thermal non-tumescent ablation technique worldwide, because it is easily applicable and repeatable. Scheduled follow up with DUS after four to six weeks and additional injections, if needed, are an essential aspect of a UGFS strategy.¹⁶⁴ Mainly for saphenous trunks < 6 mm in diameter, UGFS is considered to be a valuable alternative, provided the use of an adequate injection strategy (i.e., several injections of foam along the target vein, instead of just one injection distally).

Very large GSVs (with a diameter > 12mm) may be treated effectively with EVTA,²⁸⁶ without the need for high ligation, even if HLS remains a valid alternative (see subsection 4.6.8.1). Apart from very exceptional cases, such as large GSV aneurysms close to the SFJ (see subsection 4.6.8.4), there is no indication for adding high ligation to EVTA.¹²⁷

4.6.2. Small saphenous vein incompetence

Incompetence of the SSV represents a significant burden of disease with associated debilitating symptomatology.²⁸⁷ Ligation of the SPJ with or without stripping of the proximal SSV (open SSV surgery) has long represented the standard of care in this cohort. However, operative dissection is often rendered challenging by the variable anatomy of the SPJ, with extensive anatomical exposures predisposing to a higher risk of neurological morbidity.²⁸⁸ On the other hand, poor visualisation of junctional anatomy and inadequate control of reflux points increase the risk of subsequent recurrence. As a result, endovenous strategies are advocated increasingly to replace surgery in the management of SSV reflux (Fig. 8).²⁸⁹

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Figure 8. Interventional treatment options for patients with symptomatic small saphenous vein (SSV) incompetence. Alternative strategies, with preservation of the SSV trunk (CHIVA, ASVAL), have not been included in this flowchart. ∗Ultrasound-guided foam sclerotherapy (UGFS) only if SSV diameter is <6 mm. EVTA = endovenous thermal ablation; CAC = cyanoacrylate closure; MOCA = mechanochemical ablation; CHIVA = ambulatory conservative haemodynamic treatment of venous incompetence in outpatients; ASVAL = ambulatory selective varices ablation under local anaesthesia.

In a Cochrane review, data from three RCTs,290, 291, 292 examining the outcomes of 311 participants undergoing either SSV EVLA or open surgery were studied.²⁹³ One year ultrasound recurrence statistically significantly favoured EVLA (pooled odds ratio = 0.24, 95% CI 0.07 – 0.77, p = .016). No differences in early QoL and rate of DVT were identified between groups. Sural nerve injury was commonly identified and notably higher in the open surgery cohort (28.8% vs. 6.8%).²⁹³ This risk may be precluded further by SSV puncture at midcalf level, with lower access points at the lateral malleolus associated with higher rates of post-procedural pain and neuropathy because of sural nerve injury.¹⁴² Alternatively sural nerve hydrodisplacement may reduce rates of sural nerve injury in those requiring more distal SSV intervention.²⁹⁴

Further meta-analysis,²⁸⁸ of 49 observational studies (including five RCTs) reported procedural occlusion rates of the various SSV interventions as follows; EVLA 98.5%, RFA 97.1%, UGFS 63.6%, open SSV surgery 58%. Early reports of the efficacy of other non-thermal non-tumescent ablative procedures for SSV incompetence (CAC, MOCA) are yet to be supported by additional long term RCTs, to reach a higher level of evidence.208, 209, 210

For patients with SSV incompetence, treatment strategy should be based on shared decision making, as for the GSV. In view of the above mentioned evidence, EVTA is the first choice treatment modality. Non-thermal non-tumescent techniques, including UGFS, may be a valid alternative and open SSV surgery can still be an option if other techniques are not available (Fig. 8).

4.6.3. Anterior accessory saphenous vein incompetence

Isolated AASV reflux accounts for 10% of symptomatic presentations of patients with VVs.²⁹⁵ The AASV has a relatively short course (5 – 20 cm from the SFJ) and its incompetence manifests clinically as VVs of the anterolateral thigh, lateral knee, and lower leg (Fig. 4). AASV incompetence has morbidity rates similar to isolated GSV incompetence.²⁹⁶ Between 8% and 32% of limbs with ablated GSVs may subsequently develop AASV reflux.^297,298

Multiple strategic approaches have been described to treat AASV incompetence; however, supportive trial data are sparse.²⁹⁹ While retrospective reports^300,301 identify recurrence rates of 1.6% – 36% associated with open surgery (HLS or ligation and short excision of the AASV), this approach has been largely superseded by endovenous intervention.^127,299 In two prospective reports the outcomes of 206 accessory trunks undergoing EVLA with or without UGFS were studied: both found closure rates of 100% and significant improvements in QoL.^302,303 Similarly, a recanalisation rate of 3.6% at 28 months was identified among 139 saphenous trunks, treated with UGFS alone.³⁰⁴ Most recently, a small series has suggested the early efficacy of AASV CAC.²³⁴ MOCA modalities are yet to be definitively examined; however, given the proven efficacy of non-tumescent non-thermal techniques elsewhere, its effects are probably transferable to alternative saphenous trunks with further data required.

An alternative strategy for patients with symptomatic AASV incompetence consists of performing single ambulatory phlebectomies, without high ligation (see subsection 4.6.7.2). In a small prospective study (65 patients) with one year follow up, this approach appeared to be efficacious and safe. The mean diameter of the AASV significantly reduced (from 6.4 to 3.4 mm) and AASV reflux was abolished in 82% of treated limbs.³⁰⁵

The treatment strategy for patients with AASV incompetence is summarised in Fig. 9.

Recommendation 46		New
For patients with incompetence of the anterior accessory saphenous vein requiring treatment, endovenous thermal ablation should be considered.
Class	Level	References	ToE
IIa	C	Theivacumar et al. (2009),302 King et al. (2009)303

Recommendation 47		New
For patients with incompetence of the anterior accessory saphenous vein requiring treatment, ultrasound guided foam sclerotherapy may be considered.
Class	Level	References	ToE
IIb	C	Bradbury et al. (2010)304

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Figure 9. Interventional treatment options for patients with symptomatic anterior accessory saphenous vein (AASV) incompetence. Alternative strategies, with preservation of the AASV trunk (CHIVA, ASVAL), have not been included in this flowchart. ∗Ultrasound-guided foam sclerotherapy (UGFS) only if AASV diameter is <6 mm. EVTA = endovenous thermal ablation; CAC = cyanoacrylate closure; MOCA = mechanochemical ablation; CHIVA = ambulatory conservative haemodynamic treatment of venous incompetence in outpatients; ASVAL = ambulatory selective varices ablation under local anaesthesia.

4.6.4. Concomitant versus delayed phlebectomies/sclerotherapy

Endovenous ablation procedures may be performed as single interventions on the incompetent saphenous trunks, followed by delayed tributary treatment if needed, or with concomitant phlebectomies or foam sclerotherapy of tributaries.^252,306 The optimal timing of tributary treatment remains unclear and objective testing to assess cohorts who will benefit from adjunctive phlebectomy is lacking.

On one hand, several studies have shown that, after any type of truncal ablation, many tributaries collapse spontaneously after an interval of six weeks to six months.^234,306,307 Nevertheless the durability of this initial result, and in particular the need for re-intervention in the long term, has not been studied extensively.³⁰⁸ On the other hand, concomitant treatment reduces the need for subsequent treatment of residual tributaries, as has been demonstrated in several RCTs and a meta-analysis.³⁰⁹ In the AVULS study, 36% of patients required a secondary treatment of tributaries in the EVTA alone group versus 2% in the EVTA plus simultaneous phlebectomies group (p < .001).³⁰⁶ A previously performed, smaller RCT (50 patients) had shown rates of 66% and 4%, respectively.²³⁷ Initially, concomitant phlebectomies resulted in improved VCSS and QoL (AVVQ) scores, but this effect had disappeared after one year and remained the same after five years.^237,306,310 Another multicentre RCT has shown that foam sclerotherapy in combination with EVTA provided improvement in symptoms and QoL as well as patient and physician assessed appearance (p < .05), and reduced the need for additional treatment (p < .05).²⁴⁷ With regard to the risk of VTE, meta-analysis outcomes have identified similar rates of peri-procedural DVT (2.8% vs. 1.8%, p = .31) associated with both concomitant and staged approaches, respectively.³⁰⁹

For patients with incompetent GSV and SSV, with refluxing varicose tributaries, the treatment strategy for the latter (Figure 7, Figure 8) should be based on shared decision making, taking into account the potential advantages and disadvantages of concomitant versus delayed treatment. As the length of the AASV is usually rather short and the visible VVs often extend below the knee, concomitant tributary treatment is considered in most of these cases (Fig. 9).

4.6.5. Incompetence of other superficial veins

The incorporation of routine DUS into modern treatment strategies has broadened the understanding of atypical reflux sources. To date prospective data examining their management is limited, with little therapeutic consensus.

4.6.6. Perforating vein incompetence

In an initial stage of CVD (C2 – C3), PVs may act as a re-entry point for superficial venous incompetence, and present a net inward flow during a compression-release manoeuvre.²⁹⁵ In such cases, treatment of refluxing trunks and tributaries is usually sufficient, as re-entry PVs tend to become competent again after such treatment.^316,317 Treatment of PVs is only indicated in rare cases of isolated PV incompetence, directly responsible for clinically relevant VVs, such as those related to an incompetent midthigh PV of the FV or a popliteal fossa PV. Residual incompetent PVs, after previous truncal vein ablation, may be another indication for treatment, in particular in cases of skin changes. Also, in recurrent VVs treatment of incompetent PVs may be important (see subsection 4.7.3), and it is also an integral part of the CHIVA concept (see subsection 4.6.7.1).

Treatment of PV incompetence has been studied specifically when related to advanced skin changes (CVD clinical CEAP class C4b, C5) and in particular to VLU. Often, the term “pathological PVs” has been used, defined as those near or adjacent to a healed or open VLU demonstrating reflux > 0.5 seconds and measuring ≥ 3.5 mm in diameter.³¹⁸ In a multicentre prospective cohort study, 125 pathological PVs were treated in 83 patients using 1470 nm EVLA (400 μm optical fibre), resulting in a 71.3% closure rate and good clinical results after 12 months.²⁶¹ A retrospective study suggested improved VLU healing associated with a combination of truncal and PV EVLA versus truncal ablation alone.²⁵³ In a post hoc analysis of 97 patients undergoing surgery for both truncal and PV incompetence (including SEPS), as part of a RCT comparing surgery with conservative treatment,³¹⁹ the authors found more recurrent VLUs (C6r) in cases in which PV ligation or division had been incomplete.²⁵⁴ However, it should be acknowledged that the role of SEPS for VLU treatment remains uncertain. In a Cochrane Database systematic review on this topic, only four mainly small and poorly reported RCTs could be included and the authors concluded that they were unable to determine the potential benefits and harms of SEPS.²⁶⁴ Comparisons of treatment modalities for PV incompetence are scarce and no difference in VLU healing was found in a recent study.³²⁰

4.6.7. Preservation of the saphenous trunk

An improved understanding of flow dynamics, based on detailed DUS, has led to the emergence of saphenous sparing strategies to treat patients with varicose veins without removing or ablating the incompetent saphenous trunk: CHIVA, a French acronym for: “Cure Conservatrice et Hémodynamique de l’Insuffisance Veineuse en Ambulatoire” (conservative and haemodynamic treatment of venous incompetence in outpatients) and ASVAL (Ambulatory Selective Varicose vein Ablation under Local Anaesthesia).

4.6.8. Special anatomical considerations

4.7.1. Aetiology and risk factors

4.7.2. Prevention

Regardless of the choice of intervention modality, detailed pre-operative DUS imaging has been shown to improve the results of VV surgery based on correct identification of incompetence in the GSV, AASV, and/or SSV system.⁴³ Traditionally, for HLS, flush ligation of the GSV is performed at its junction with the CFV, together with ligation of all tributaries of the SFJ, to minimise the risk of groin recurrence.

To reduce the incidence of neovascularisation, several techniques have been investigated. A RCT proved that oversewing the SFJ stump to close the endothelial funnel and avoid contact with the surrounding subcutaneous tissue reduced the development of recurrent reflux.³⁴² Other studies reported good results of implantation of a prosthetic patch or closure of the cribriform fascia to contain neovascularisation at the SFJ.^343,344

When EVTA is offered, meticulous ultrasound guidance is mandatory to reduce recurrence, similar to other techniques. The ablated length of GSV should be determined by the lowest refluxing tributary, with higher rates of re-intervention associated with inadequate ablation length.³⁴⁵ However, in a minority of cases, GSV ablation in the calf may result in saphenous nerve injury and this risk must be considered carefully in the context of disease severity. In these cases, adjunctive below knee UGFS with above knee thermal ablation may reduce this risk.³⁴⁵ Another approach is to use an alternative non-thermal technique, such as MOCA or CAC, if ablation below midcalf is warranted. To minimise the risk of residual or newly developed reflux in SFJ tributaries and accessory veins (mainly the AASV), it has been proposed to position the tip of a radial laser fibre exactly at the SFJ (see subsection 4.2.1.2), but evidence about the benefits and safety of such strategy is still lacking.¹⁷⁸

4.7.3. Treatment

In the past, recurrent VVs were mainly treated by redo open surgery. Open exploration of the groin or popliteal fossa through scar tissue takes longer and has a higher complication rate, as well as increased lymphatic leakage and wound infections; therefore, it should be avoided whenever possible.^346,347 A less invasive approach, such as EVTA or non-thermal ablation of an incompetent saphenous trunk, UGFS, or multiple phlebectomies without groin re-exploration, has been advocated to replace invasive redo surgery. These procedures are deemed to be safe and as effective as redo surgery.³⁴⁶ To determine the most suitable technique, detailed DUS mapping is mandatory.

Several studies have described the use of EVTA as a safe and effective option for the treatment of recurrent VVs, in the presence of a recurrent or residual incompetent saphenous trunk.348, 349, 350, 351, 352 A small RCT compared redo surgery with RFA and found that the latter was superior, with lower pain scores, bruising, and procedure times.³⁵¹ In two retrospective studies, in which EVLA of the GSV and the SSV was compared with open redo surgery, the re-recurrence and complication rates were lower in the EVLA groups.^348,349 In particular, sural nerve neuralgia was less common after EVLA than after SSV redo surgery (9% vs. 20%).³⁴⁸

UGFS is the most widely used treatment for all kinds of recurrent VVs, including VVs associated with incompetent PVs or lymph node venous networks¹⁶ near the SFJ. The technique is minimally invasive, well tolerated by the patients, does not require anaesthesia, and can be repeated easily.³⁵³ The reported success rates at one year follow up range from 87% to 91% for recurrent saphenous truncal reflux.³⁵⁴ In a large prospective cohort study, 142 cases of recurrent VVs related to groin neovascularisation, 155 inguinal recurrences related to residual SFJ stump, and 28 popliteal recurrences related to residual SPJ stump were treated with UGFS. After a mean follow up of 4.4 years, only 20% of treated patients had developed a new clinical recurrence.³⁵³ In conclusion, UGFS is a widely applicable technique in patients with recurrent VVs, especially in the presence of neovascularisation and tortuous tributaries. Foam injections can be combined with other techniques (EVTA, phlebectomies) to eliminate multiple sources of reflux during the same session or subsequently.

5.2.1. Specialised care

Ideally, invasive treatment should be performed in centres with a high level of expertise, after carefully weighing the pros and cons of intervention, given the considerable learning curve associated with these procedures.

5.2.2. Anaesthesia

Recanalisation of obstructed deep veins may take time, and venous dilation and stenting is painful. This should therefore be done under sedation, combined with intravenous analgesia in patients with a NIVL, and under general anaesthesia in patients with post-thrombotic fibrotic lesions, which require a more complex procedure (sometimes combined with endophlebectomy in the groin, see subsection 5.3.2.7). Interventions for deep vein reflux are delicate and time consuming, and should be performed under general anaesthesia.

5.2.3. Compression after treatment

Leg compression is usually prescribed after deep venous procedures but there are scarce data on its effectiveness. However, compression therapy is recommended when symptoms persist after invasive treatment (see subsection 3.2 and Fig. 6).

5.3.1. Indications for treatment

Treatment of asymptomatic individuals, even with high grade stenosis or occlusion, is not supported by any robust evidence that suggests this reduces the risk of subsequent DVT or PE.

In symptomatic patients, the indications to treat CVD by endovascular recanalisation vary between studies. Clinical selection and reporting of patients has usually been based on the CEAP classification, the Villalta scale and the r-VCSS (see subsection 1.5).³⁵⁹ The clinical class C3 – C6 of the CEAP classification at baseline is the most commonly used criterion for considering intervention. Second, the Villalta scale has become the gold standard used to diagnose PTS and is therefore also used for selection of patients with moderate (Villalta score 10 – 14) or severe PTS (Villalta score ≥ 15, or VLU). Venous claudication, usually described as heaviness and pain during exercise subsiding during rest, is a non-objective and poorly validated symptom.³² It is not included in formal scoring systems, but it may be one of the most meaningful indications for intervention in chronic outflow obstruction.

In addition to clinical assessment, arbitrary cutoff values on venography, CTV, MRV, and/or IVUS, most often of at least 50% lumen narrowing, have been used.359, 360, 361 Plethysmographic methods have been used in some centres to identify patients who would benefit from deep venous stenting, but these are still debated.362, 363, 364

5.3.2. Iliocaval and iliofemoral obstruction

Both intra- and extraluminal causes of iliocaval and iliofemoral outflow obstruction can be treated by endovascular procedures. In some exceptional cases, only the IVC is obstructed. This may be post-thrombotic or result from “congenital absence” of the IVC (also known as vena cava atresia). The latter may also be caused by DVT in the neonatal period or at a very young age. Even in such cases, recanalisation may be possible, although this can be a very challenging procedure.

5.3.3. Femoropopliteal obstruction

5.3.4. Antithrombotic treatment

Peri- and post-operative antithrombotic treatment is crucial, but the use of the various regimens is heterogeneous among studies.³⁵⁵ Neither type of anticoagulation nor duration have been studied prospectively. In a single centre retrospective study of 154 PTS patients undergoing iliofemoral venous stenting, rivaroxaban exhibited similar safety but superior efficacy to warfarin.³⁸⁹ Close collaboration with a haematologist is often warranted, to decide on an individualised anti-thrombotic treatment strategy.

Patients on anticoagulants should be bridged to LMWH pre-operatively and continue treatment after the procedure. Peri-operatively, all patients should be adequately heparinised. Patients on indefinite anticoagulation (vitamin K antagonists or DOACs) before the procedure, should continue anticoagulation after the procedure, unless major bleeding complications occur. If there is no indication for indefinite anticoagulation, post-operative anticoagulation should be prescribed, but there is insufficient evidence to guide decision making regarding the optimum duration. According to experts participating in a Delphi consensus, anticoagulant treatment should be continued for at least six months after intervention in patients with a history of DVT. Regarding the role of antiplatelets, no consensus was reached.³⁹⁰

In addition to antithrombotic treatment, use of an IPC during and immediately after the procedure, and early mobilisation may help to reduce thrombotic complications after deep venous interventions but, as with the above strategies, there is a paucity of evidence. Also, in patients undergoing stenting for NIVL, there is a lack of evidence to guide antithrombotic strategies and hence no particular strategy can be recommended.

5.3.5. Safety issues

Peri-operative death and PE are extremely rare after deep venous interventions and reports of this complication are sparse. The overall rate of complications was 3% in one study involving almost 4 000 stented limbs.³⁵⁵ Complications include access site haematoma, stent migration or fracture, iliac vein rupture, stent thrombosis, and contralateral DVT. The incidence of contralateral DVT varies from 0% to 15.6% among studies. It usually results from stenting into the IVC, which is often unavoidable, thereby jailing the contralateral iliac vein.³⁹¹

5.3.6. Multidisciplinary team

It is strongly suggested that patients undergoing intervention for iliac venous obstruction, in particular those with PTS, are managed within a multidisciplinary team. This team should consist principally of an interventional radiologist, a vascular surgeon, and a haematologist (with a specified interest in thrombosis). Other specialists may be added to the team as necessary.

6.1.1. Specialist care

In recent years, the trend towards a multidisciplinary approach to chronic wound care has led to better diagnostic procedures and clinical outcomes.⁴¹² The introduction of a systematic approach to wound management in 2003, known as the “TIME” (Tissue, Infection/inflammation, Moisture balance and Edge of wound) concept, has been considered a potentially useful tool.^413,414 Despite a lack of RCTs, the TIME principles are widely adopted for the treatment of VLUs.

6.1.2. Pain control

Pain is a significant complaint for patients with VLUs. Patients most commonly describe wound related background pain and pain related to dressing changes and wound procedures.⁴¹⁵ A pain assessment should include location, severity, quality/characteristics, frequency, and timing. Triggers, effective relievers, and the impact of pain on QoL and functional ability should also be recorded. There are several pain assessment tools in use but the visual analogue scale (VAS) is the most often applied.⁴¹¹ A recent meta-analysis of 36 publications showed that the prevalence of wound related background pain in patients with VLUs (from 10 studies) was 80% (95% CI 65% – 92%) and the mean pain intensity score (from 27 studies) was 4 (95% CI 3.4 – 4.5) on a 0 – 10 VAS scale.⁴¹⁶ A systematic review found no trials evaluating interventions for persistent pain in VLU patients.⁴¹⁷ However, a eutectic mixture of local anaesthetic (EMLA cream) was found to be superior to placebo in controlling pain during wound debridement (mean difference −20.65 on a 100 mm VAS, 95% CI −12.19 – −29.11). In terms of general principles, the three step analgesic ladder developed by the World Health Organization for management of cancer and chronic pain is an effective approach.⁴¹⁵

6.1.3. Antibiotics and antiseptics

Colonisation of VLUs by bacteria is common and of little clinical significance, but the presence of infection may delay ulcer healing. Systemic antibiotics and topical antibiotics or antiseptics have been proposed for treatment of clinical infection in VLUs. The evidence from a Cochrane review suggests that routine use of systemic antimicrobials is not beneficial for VLUs.⁴¹⁸ In terms of topical preparations, there is no evidence to support the efficacy of topical antibiotics. Therefore, the practice of taking routine bacteriological swabs from leg ulcers is not recommended. The pooled estimate from 11 RCTs showed that more VLUs healed when treated with topical cadexomer iodine (an antiseptic) compared with the standard care at four to 12 weeks (RR 2.17, 95% CI 1.30 – 3.60). Systematic reviews have also suggested that silver dressings (with recognised antimicrobial effects) may increase the probability of VLU healing (RR 2.43, 95% CI 1.58 – 3.74),⁴¹⁹ although further studies evaluating time to complete wound healing (rather than healing rate) are needed.⁴²⁰

6.1.4. Mobilisation and physical therapy

The aim of mobilisation and physical therapy in patients with VLUs is to decrease venous hypertension and oedema (see subsection 3.1). This can be achieved through activation of the calf muscle pump by specific exercises of the ankle or by biomechanical stimulation of the calf muscle pump. Although beneficial in principle, studies demonstrating improved VLU healing or reduction of recurrence rate with exercise or specific physical therapy are scarce.

6.1.5. Comorbidities

Patients with VLUs are often elderly and co-existent comorbidities are common.⁴²¹ Ankle stiffness (resulting in calf muscle pump failure) and obesity are common causes of venous hypertension (see subsections 3.1 and 8.2.1, respectively). Optimisation of systemic medical issues should be considered to promote wound healing. The presence of lower extremity atherosclerotic disease is particularly relevant, so a basic assessment of arterial status (continuous wave Doppler, to measure ankle pressure and ABI) should be performed. An ABI > 0.8 may be considered as normal and allows commencement of full compression therapy.⁴²² In patients with diabetes and incompressible arteries, evaluation using arterial DUS or toe pressure may be required to exclude arterial disease. Modified compression may be beneficial in patients with mixed arterial and venous ulceration (see subsection 6.3.3).

6.2.1. Debridement

Wound debridement describes the removal of necrotic tissue, debris, or foreign bodies from a wound.⁴²⁴ It should be preceded by wound cleansing, defined as the “removal of surface contaminants, bacteria and remnants of previous dressings from the wound surface and its surrounding skin”.⁴²⁵ Methods for wound debridement include:

•

surgical/sharp debridement

•

mechanical debridement (washing solutions, whirlpool therapy, wet to dry dressings, ultrasound assisted debridement and lavage)

•

enzymatic debridement (topical application of enzymes breaks down the tissue attaching necrotic tissue to the wound bed)

•

autolytic debridement (application of dressings facilitates development of the body’s own enzymes to rid a wound of necrotic tissue)

•

biosurgical debridement (sterile larvae).

A Cochrane review identified 10 RCTs involving 715 participants with VLUs and several debridement strategies were studied.⁴²⁶ The authors concluded that there was limited evidence that active debridement of a VLU has a significant impact on healing. However, this conclusion was based on low quality (and quantity) evidence, so larger trials are required.

6.2.2. Dressings and topical agents

A large number of types of wound dressings are in current use for VLUs. A recent Cochrane review and network meta-analysis included 59 RCTs (5 156 participants) and concluded that more research is needed to evaluate whether VLU healing is improved by any particular dressings or topical agents.⁴¹⁹ Similarly, another Cochrane review including 12 studies of protease modulating matrix treatment concluded that the quality of evidence was too low to demonstrate whether ulcer healing or adverse events are influenced by this local treatment.⁴²⁷ Despite this, specific dressings are likely to be useful in management of specific wound characteristics (such as excessive exudate). There is a lack of reliable evidence supporting the use of hyperbaric oxygen therapy to improve VLU healing.⁴²⁸

6.2.3. Other wound therapies

6.3.1. Compression materials

Compression for VLU treatment can be applied by means of ECS, superimposed ECS, elastic bandages and IB, ACG, and IPC (see subsection 3.2). Superimposed ECS are mainly used for small VLUs (area < 5 cm²). The inner stocking keeps the ulcer dressing in place and is removed only at dressing changes. It can be worn day and night, as the sustained low pressure of 20 mmHg is well tolerated, even in the supine position. The second stocking exerting 20 – 25 mmHg is worn on top of the inner stocking during the daytime. The complete kit exerts a pressure of around 40 mmHg in the supine position rising to almost 50 mmHg in upright position, which is useful to promote VLU healing. Inelastic bandages are mostly applied as multicomponent, multilayer bandages, which are superimposed. This makes the final bandage totally inelastic, according to objective measurements. The best indicator of the elastic characteristics of a compression system is the “static stiffness index” (SSI), which is obtained by calculating the difference between standing and supine pressure (in mmHg).⁴³⁴ The SSI of IB is always > 10 mmHg, while elastic material shows a SSI < 10 mmHg. The SSI of the so called “four layer” bandages (consisting of four elastic bandages) appeared to be in the range of IB (> 10 mmHg).⁴³⁵ This is mainly because of the friction produced by superimposing the four components of this multicomponent, multilayer bandage (resulting in more than 10 layers if applied properly).

In recent years, ACG have increased in popularity, also for patients with VLU, and could represent an increasingly interesting option for the future. ACG are manufactured with inelastic material and are similar to IB in terms of pressure and stiffness. While applying ECS, superimposed ECS or ACG is relatively simple, wrapping IB in the correct way providing the necessary strong pressure is not easy.⁴³⁶ For IB, the compression pressure is not determined by the material, but depends on the stretch applied during bandaging and on how the different turns are superimposed.

6.3.2. Haemodynamic and clinical effects in patients with venous leg ulceration

Inelastic materials have been shown to be more effective than elastic materials in reducing venous reflux and increasing venous pump function, thereby improving venous haemodynamics.⁴³⁷ Inelastic compression by multicomponent, multilayer bandages or ACG, exerting a high pressure ≥ 40 mmHg,438, 439, 440 should be applied in VLU treatment. In small VLUs, superimposed ECS may be a good alternative, as was obvious from a large RCT, including 457 participants with VLU, randomised between superimposed ECS and four layer bandage.⁴⁴⁰ In this study, the median ulcer area was small (3.9 cm², interquartile range [IQR] 1.6, 8.7) and the median ulcer duration was four months (IQR 2, 11 months). Median time to ulcer healing was 99 days (95% CI 84 – 126) in the superimposed ECS group and 98 days (95% CI 85 – 112) in the bandage group.

ACG can be applied with high pressure and high stiffness and are haemodynamically very effective as they are able to maintain their compression pressure. When compared with IB, ACG were demonstrated to be even more effective for VLU healing.^441,442 ACG are also more cost effective and have the advantage of allowing self management.⁴⁴²

IPC increases VLU healing compared with no compression but was not shown to be more effective than other compression modalities when used as single treatment. There is limited evidence, based on a small RCT, demonstrating that IPC may improve the VLU healing rate when used in addition to standard compression.⁴⁴³ In clinical practice, IPC is used in VLU treatment as a single treatment or in association with other kinds of compression. It is mainly indicated when other compression methods cannot be applied because of problems with patient compliance or because they fail to improve VLU healing.

6.3.3. Treatment of mixed venous and arterial ulcers

In about 15% – 20% of VLU, the patients also suffer from arterial disease of the affected leg, with an ABI < 0.8.^444,445 The role of compression therapy for patients with ABI < 0.8 is controversial as there is thought to be a greater risk of iatrogenic skin damage with the use of compression therapy in the presence of arterial disease. However, it has been demonstrated that modified compression therapy, using short stretch material with a pressure ≤ 40 mmHg, is very effective in obtaining healing of a mixed ulcer, provided the absolute value of the ankle pressure is > 60 mmHg, the toe pressure > 30 mmHg and the ABI > 0.6 (see contraindications for compression, Table 7). If these conditions are respected, mixed ulcers eventually heal, although with some delay compared with VLUs.^446,447 Close clinical supervision is mandatory when using compression therapy in patients with mixed arterial and venous disease and compression should be discontinued immediately if ulceration deteriorates or if the leg is very painful after applying the bandage. For an ankle pressure < 60 mmHg, a toe pressure < 30 mmHg, or an ABI < 0.6, sustained compression therapy should be avoided in most cases and arterial revascularisation should be considered.⁴⁴⁴

6.3.4. Prevention of ulcer recurrence

For the majority of VLU patients, correction of superficial venous incompetence (see subsection 6.4) and/or underlying deep venous pathology (see subsection 6.5) are essential tools to prevent VLU recurrence. Alternatively, a conservative approach, consisting of compression therapy using below knee ECS may be useful to prevent ulcer recurrence. The higher the compression pressure, the lower the ulcer recurrence rate;⁴⁴⁸ however, it should also be acknowledged that the higher the pressure, the lower the compliance.⁹⁰ It has been reported that the lowest VLU recurrence rates were seen in patients who were compliant with hosiery regardless of the compression level.⁴⁴⁹

6.4.1. Rationale for superficial venous interventions in venous ulceration

Chronic venous hypertension is accepted as the underlying pathophysiological cause of the skin damage that results in VLU with several potential contributing factors. General measures such as effective compression and elevation are important and should be advised wherever possible. However, superficial venous reflux is a very common finding and is usually an important factor contributing to venous skin damage, even in the presence of other pathologies. Several RCTs have demonstrated clinical advantages (improved VLU healing and reduced recurrence) with treatment of superficial venous reflux in patients with VLU.^451,452 There is a clear logic to treatment of the underlying cause of the chronic venous hypertension. Randomised studies have shown that improved outcomes after treatment of superficial reflux are seen, even when concomitant deep venous reflux is present, indicating that deep reflux should not be considered a contraindication to superficial venous intervention.^451,452

6.4.2. Timing of interventions

For patients with VLUs and superficial venous reflux, it would seem logical to address the underlying pathophysiology as soon as possible to deliver maximum clinical benefit. However, the evidence to support this rational strategy has been lacking until recently. In the multicentre “Early Venous Reflux Ablation” (EVRA) study, 450 participants with VLUs (between six weeks and six months duration) and superficial venous reflux were randomised to compression with early endovenous reflux ablation within two weeks, or compression with deferred ablation of superficial reflux, once the ulcer had healed. Early endovenous ablation accelerated VLU healing with 24 week healing rates of 85.6% and 75.4% in early and deferred intervention groups, respectively (p < .001).⁴⁵¹ These findings suggest that prompt ablation of superficial reflux reduces venous hypertension over and above compression therapy alone. Long term findings showed that overall ulcer recurrence was lower in the early intervention group.⁴⁵³ It should be noted that patients in the EVRA trial had ulcers of less than six months duration and trial participants had a high level of compliance with compression therapy, which is not usually the case in real world practice. However, most would argue that for patients with chronic VLU of greater than six months duration, or those unable to tolerate compression therapy, aggressive and early ablation of the underlying pathological reflux is even more important.

Other RCTs have also evaluated the clinical benefits of superficial venous intervention in patients with VLU. In the ESCHAR trial (Effect of Surgery and Compression on Healing and Recurrence trial), 500 patients with active, or recently healed, VLU were randomised to compression alone, or compression with open superficial venous surgery. Surgical interventions were performed at a median of seven weeks post-randomisation and, although there was no difference in VLU healing rates, lower VLU recurrence rates were seen in the intervention group (four year VLU recurrence rates of 31% vs. 56%). Other studies including patients with VLU, e.g.; the Dutch SEPS^319,454 and USABLE⁴⁵⁵ trials, also demonstrated excellent outcomes after intervention for superficial reflux, although there were no statistically significant benefits when compared with compression alone.

In many healthcare systems, VLU care is delivered mainly in primary care settings, without easy or prompt access to tools for assessment or treatment of venous disease. Therefore, a pragmatic approach should be adopted where assessment and ablation of superficial venous reflux are performed as quickly as possible, and ideally within two weeks.

6.4.3. Choice of superficial venous intervention

As described in Chapter 4, there are a large number of endovenous and surgical treatment modalities for the ablation of refluxing superficial veins. In the ESCHAR trial, traditional superficial venous surgery (including SFJ/SPJ ligation alone) were used. In the Dutch SEPS trial, a combination of open surgery and SEPS were performed. In recent years, open surgical interventions have been superseded by endovenous interventions. These minimally invasive procedures, performed using tumescent anaesthesia alone, can be used for the entire population with VLUs. In the EVRA study, only endovenous ablation procedures (thermal ablation, non-thermal ablation or UGFS) were allowed. The choice of modality was left to the discretion of the treating physician. Subgroup analyses showed similar healing improvements irrespective of the modality. Therefore, selection of endovenous intervention should be guided by physician skill/experience and patient choice (see subsection 4.6).

The management of incompetent PVs in patients with VLUs is a source of considerable controversy and variation in practice (see subsection 4.6.6). It is common to identify pathological PVs in limbs with C6 disease, usually in combination with truncal saphenous reflux. In the ESCHAR trial, the superficial venous intervention targeted the truncal saphenous reflux only. In the EVRA study, no specific perforator interventions were performed, although most participants were treated with UGFS, so some perforators may have been ablated indirectly. There are no RCTs demonstrating additional benefit from concomitant PV intervention, although persisting incompetent PVs were associated with recurrent ulceration in one study with 10 years follow up.⁴⁵⁴ To date, the experience with endovenous treatment of PV incompetence (mainly of PVs close to the diseased skin), in combination with truncal thermal ablation, remains limited in patients with VLU.^253,261 Although there may be a pragmatic logic to aggressive intervention for incompetent PVs, such interventions may be challenging, evidence for the additional benefit of PV ablation (over and above truncal ablation) is weak and previous guidelines only offer minor support for such an approach.³⁸³

6.4.4. Treatment of the sub-ulcer venous plexus

The frequent presence of a leash of small, incompetent tributaries under a VLU has led to the hypothesis that this plexus of veins plays an important role in transmitting the venous hypertension to the soft tissues and skin, directly contributing to ulceration. Ablation of this venous plexus using foam sclerotherapy has been proposed as a logical approach and has been used in isolation,456, 457, 458 or in combination with saphenous vein ablation procedures.^451,459 Even if UGFS of the sub-ulcer venous plexus is a commonly used approach in clinical practice, well performed studies clearly demonstrating its additional benefit are lacking.

7.1.1. Primary sources of incompetence

PVI can originate from the left or right gonadal vein (ovarian or testicular vein), from the left or right IIV, or from a combination of these veins. Incompetent pelvic veins can be connected with perineal or vulvar veins, with veins of the proximal thigh, or with the sciatic vein, causing lower limb VVs.

7.1.2. Associated pathologies

PVI can be secondary to compression of the left CIV by the right common iliac artery (previously known as “May-Thurner syndrome”), which can cause flow reversal (reflux) in the left IIV, resultant pelvic venous hypertension, and subsequently VVs of the lower limb, with or without pelvic symptoms. Extrinsic compression may also be caused by endometriosis, or a tumour mass. Similar pressure and flow patterns may be seen frequently in cases of post-thrombotic iliac obstruction. Another rare venous compression entity, namely left renal vein (LRV) compression may also occur (previously known as “nutcracker syndrome”), in which the LRV is compressed between the aorta and the superior mesenteric artery, resulting in increased venous pressure, which may be relieved through perirenal collaterals and/or the left gonadal vein, with reflux into the pelvis and beyond.⁴⁶⁶

7.2.1. Clinical presentation

PeVD caused by PVI with or without associated pathologies may clinically manifest through pelvic symptoms, especially chronic pelvic pain (CPP), dyspareunia or prolonged post-coital ache, lower extremity VVs and/or vulvar VVs, lower extremity pain and/or swelling, and left flank pain and/or haematuria.⁴⁶⁷

In women, according to a systematic review by the World Health Organization, the prevalence of CPP, characterised by non-cyclic pain lasting for at least six months, ranged from 4% to 43%, based on 18 studies including 299 740 women.⁴⁶⁸ Pelvic venous disorders accounted for 16% – 31% of these cases. The other common causes of CPP include a wide range of gynaecological disorders, especially endometriosis, pelvic inflammatory disease, adhesions, adenomyosis, and also irritable bowel syndrome, interstitial cystitis, musculoskeletal and neurological problems, often with overlapping symptoms in individual patients.^465,469 All these alternative pathologies should be ruled out before correlating CPP with PeVD.

Compression of the CIV and the LRV causing ≥ 50% area reduction, may be present in 25% – 33% and 51% – 72% of the general population, respectively. Although most patients are asymptomatic, some may develop CPP, leg oedema, venous claudication, VLU (in cases of CIV compression) or left flank pain and/or haematuria (in cases of LRV compression).⁴⁶⁵

Pelvic venous hypertension can have different pelvic floor escape points (perineal, inguinal, obturator, clitoral, inferior gluteal and superior gluteal) and cause either atypical lower extremity and vulvar VVs or more typical saphenous truncal incompetence (GSV, AASV, SSV) and related VVs. In a large study of patients with symptoms and signs of CVD in 835 limbs, the frequency of non-saphenous reflux according to DUS was 10% and in one third of the latter group this was a result of PVI, which results in an estimated frequency of 3.4%.⁴⁷⁰ This may be higher during pregnancy and in patients with persistent or recurrent VVs after previous treatment. Among patients presenting with VVs resulting from PVI, CPP has been reported in < 10%.⁴⁶⁷

Vulvar VVs can also be the result of reflux arising from the SFJ through an incompetent superficial or deep external pudendal vein, especially in pregnant women.⁴⁷¹

In men, VVs of the lower extremity or the scrotum can also be associated with PVI. They are mainly caused by IIV incompetence through obturator or internal pudendal tributaries, or to testicular vein reflux through the inguinal canal. However, they can also be related to SFJ incompetence and external pudendal vein reflux.³³⁹

7.2.2. Investigations

To investigate VVs potentially resulting from PVI, a usual full leg DUS of lower extremity veins in the upright position is necessary as well as transperineal DUS for evaluation of pelvic escape points.^50,470 Visualisation of the SFJ is obviously important, as its incompetence can be the reason for vulvar VVs. On the other hand, in patients with vulvar VVs or recurrent VVs after previous treatment, the presence of a competent SFJ may suggest underlying PVI.

Whenever PeVD are suspected, DUS of pelvic veins (abdominal and/or transvaginal) should be the first line investigation.

7.3.1. Varicose veins of pelvic origin without pelvic symptoms

Sclerotherapy, in particular UGFS, has been used extensively in VV treatment to eliminate tributary VVs and incompetent PVs.¹⁴³ As pelvic escape points play the same role as PVs, UGFS is an adequate method for treating upper thigh and vulvar VVs of pelvic origin, in patients without pelvic symptoms. Moreover, by accessing pelvic escape points, sclerosant foam may also reach the peri-uterine venous plexus. The effectiveness of limited direct treatment of lower extremity and vulvar VVs using UGFS has been reported in several studies.^467,471 Pelvic escape points may also be eliminated by surgical ligation, which can be an alternative to sclerotherapy. In one study on 273 pelvic escape points, recurrent reflux was detected in only 2.2% after ligation.⁴⁷⁷ Phlebectomy of VVs resulting from PVI may also be performed with good clinical results.⁴⁷¹

The need for pelvic vein treatment in patients with VVs resulting from PeVD without pelvic symptoms has not been established reliably. None of the available studies has compared the outcome of treatment limited to VVs of the lower extremity and pelvic escape points with pelvic vein treatment alone in these patients. Published studies have failed to demonstrate substantial improvement in lower extremity VVs after pelvic embolisation or stenting.478, 479, 480 A prospective study in 102 patients with PVI and VVs reported mild or moderate improvement of VVs in only 51% of patients after ovarian or IIV embolisation.⁴⁷⁹ Another prospective study showed improvement of lower extremity VVs in only 14% of 43 patients after ovarian vein embolisation. In that study, good results were obtained only for vulvar VVs, which disappeared in 88% of patients.⁴⁸⁰

In a small series of 24 patients with recurrent VVs secondary to PVI, coil and glue embolisation was performed prior to repeat surgery. At four year follow up the VV re-recurrence rate was 4.2%.⁴⁸¹ The currently available literature does not support embolisation to prevent VV recurrence.

In conclusion, patients with a good clinical response to minimally invasive procedures such as foam sclerotherapy, phlebectomy, or pelvic escape points ligation, do not require pelvic vein embolisation. If VVs recur early, or, if lower extremity symptoms do not resolve, additional pelvic vein treatment may be considered subsequently. Although in general the latter treatment is safe, it is not without potentially serious complications (e.g., coil migration into the lungs) and therefore should be used for well established indications.⁴⁸²

7.3.2. Varicose veins of pelvic origin with pelvic symptoms

Percutaneous, endovenous gonadal vein (and IIV) embolisation is the current standard procedure for CPP therapy in these patients because of its effectiveness and minimal complication profile. Technical effectiveness is estimated at 96% – 100% with a recurrence rate up to 32%, while embolisation related complications are rare and non-fatal.^{467,475,476,482}

Through a femoral, jugular, or basilic vein access, the gonadal veins are catheterised followed by venography, preferably in a reversed Trendelenburg (head up) position. A variety of embolic materials, including coils, with or without additional foam sclerotherapy, and cyanoacrylate glue have been reported in the literature. Principally, they are introduced into the most distal segment of the incompetent vein first and extended as far proximally as necessary. To date, there is no hard evidence suggesting superiority of one technique over another.⁴⁷⁴

After gonadal venography and successful embolisation, the IIVs should be evaluated to document their contribution to pelvic VVs. If reflux is identified, VVs can be individually selected and coiled. Additional injection of sclerosant foam into pelvic VVs may be useful.

To date, a validated instrument to study the effects of treatment in patients with PeVD does not exist. Nevertheless, most studies focusing on CPP report significant reduction in pain scores following embolisation.^{475,476,478,479} However, high quality RCTs on embolisation of pelvic veins to treat CPP and/or (recurrent) VVs of the lower limb are missing.

Finally, in cases where CIV obstruction is identified as the most likely underlying cause of PeVD, stenting of the relevant lesion should be considered (see subsection 5.3). For LRV compression, the indications for treatment are more controversial and a multidisciplinary approach is needed. In general, pelvic vein embolisation should be avoided for LRV compression cases.⁴⁷⁴ Other invasive treatment options may be considered in exceptional cases. While open and laparoscopic surgery are used, endovascular LRV stenting has been proposed increasingly.⁴⁶⁶ In contrast to stent placement for iliac vein compression, stenting of the LRV has been associated with a higher risk of more serious complications, of which migration of the stent to the heart or pulmonary arteries is the most feared.

In conclusion, the possibility of venous outflow obstruction needs to be critically considered in patients with CPP, before pelvic vein embolisation is performed. An inappropriate treatment strategy may have serious consequences.

7.3.3. Other treatment options

Conservative treatment options for VVs of pelvic origin include compression and hormonal therapy. Especially during pregnancy, when invasive therapy should not be performed, compression hosiery adapted for pregnant women is advised.

In several RCTs, improvement in CPP with methoxyprogesterone, goserelin, or progestin implant of etonogestrel has been reported.⁴⁶⁷ However, it is unclear if these effects are directly related to treatment of the underlying PeVD or other pathways. Also, undesirable side effects of this hormonal therapy may occur.

8.1.1. Superficial vein thrombosis

Most cases of SVT are spontaneous or after a minor local trauma, usually in patients with VVs. SVT is not always a benign condition, as thrombus may ascend and extend into the deep venous system. Patients usually present with a painful red lump or cord, with localised oedema and warmth over the affected area. DUS is mandatory to evaluate thrombus extent and to exclude concomitant DVT. If the SVT is involving only a short segment of a varicose tributary (< 5 cm), evacuation of the thrombus by puncture or through a small incision, may alleviate local pain quickly. Detailed guidelines for treatment of SVT are provided in the ESVS Clinical Practice Guidelines on Venous Thrombosis.²

8.1.2. Haemorrhage

Venous hypertension, resulting from untreated VVs, iliac outflow obstruction, or right cardiac failure, may apply excess pressure to reticular veins or telangiectasias. The overlying skin then may become thinner and blebs may form. Provided the overlying skin remains intact, it may cause only bruising, but, in case of injury, even after minor trauma, it may cause excessive bleeding which can exceptionally be fatal.³⁴ Such an event often occurs during a warm shower because of venous dilation, or it may occur while sleeping, often in elderly patients living alone. Patients with pulsatile VVs may be particularly at risk of acute haemorrhage (see subsection 8.2.4). Bleeding may also occur in a VLU.

Bleeding usually subsides with immediate elevation and external pressure. Treatment of small diameter VVs and blebs can be performed effectively with foam sclerotherapy, to avoid further bleeding.⁴⁸³ Investigation for and treatment of underlying venous incompetence, if possible, will further reduce the risk of recurrent haemorrhage.

8.2.1. Obesity

The relationship between CVD and obesity is well recognised in numerous studies. The modern epidemic of obesity is reflected in the increasing proportion of those who are obese in community and population studies on CVD.⁴⁸⁴ Obese patients are often over-represented in venous clinics. Morbidly obese patients often have lower limb skin changes and ulcers consistent with CVD.^485,486

The impact of obesity on venous haemodynamics, with increased reflux and greater venous pressures contributing to the greater CVD severity are all well described.⁴⁸⁷ The primary mechanism for this is the raised intra-abdominal pressure.⁴⁸⁸ Muscle pump deficiency has also been implicated in the obese. Despite the muscle pump of an obese patient having increased venous ejection volumes, it is used less frequently with fewer daily steps.⁴⁸⁷

Therefore, obesity is increasingly important, as it contributes to the severity of CVD and influences treatment strategies and outcomes. In a retrospective analysis including 65 329 patients undergoing EVTA, phlebectomies, and UGFS or combined treatment, inferior outcomes (r-VCSS, CIVIQ-20) were observed in patients with a BMI of ≥ 35 kg/m² compared with those having a lower BMI. However, improvements in r-VCSS and CIVIQ-20 were found in all BMI categories six months after treatment.⁴⁸⁹ If venous intervention is indicated, EVTA or non-thermal ablation of incompetent saphenous trunks is preferred over open surgery,¹²⁷ as complications such as wound infection after endovenous ablation are rare. However, cannulation and ablation may be technically demanding as veins are deeper under the skin compared with non-obese patients.

Weight loss is an effective adjunct to treatment. For those with morbid obesity, bariatric surgery improves skin problems from 75% to 80% down to 36.4% after weight loss.⁴⁸⁶ Another study compared the effect of bariatric surgery in 72 patients with morbid obesity and severe manifestations of CVI with 51 similar patients who did not have surgery. In addition to a significant drop in BMI in the surgery group, these patients showed an increased rate of VLU healing, a decrease in venous claudication, and an improvement in venous QoL.⁴⁹⁰ Weight loss, by lifestyle changes in those with less severe obesity, is recommended to achieve similar benefits (see subsection 3.1).

8.2.2. Pregnancy

Pregnancy is a contributory factor to CVD, increasing the frequency of telangiectasias, reticular veins, VVs, and recurrent SFJ reflux after VV surgery.⁴⁹¹ Leg oedema can affect up to 80% of pregnant women, mainly during the third trimester. Some women develop vulvar VVs, which tend to be exacerbated with each subsequent pregnancy (see subsection 7.2).

In pregnant women treatment of leg oedema, VVs, and vulvar VVs is mostly conservative with compression hosiery. ECS not only have a beneficial effect on GSV and SSV diameter and reflux, but also improve symptoms and signs of CVD.492, 493, 494 According to the NICE guidelines on management of VVs, interventional treatment should not be offered during pregnancy.⁴⁹⁵

In the majority of women, telangiectasias, reticular veins, and VVs subside at least partially within the first postpartum months. Any further treatment should therefore be postponed until three to six months after delivery.

8.2.3. Patients on anticoagulants

Patients receiving long term anticoagulants may be at increased risk of thromboembolic events if their medication is temporarily interrupted. Bridging may be considered, but this increases costs and adds complexity to the planning of venous interventions. On the other hand, continuing anticoagulants might increase the risk of bleeding or decrease the efficacy of the ablation.

Concerning treatment of superficial venous incompetence, the largest study on this topic included 100 EVTA procedures in 65 chronically anticoagulated patients and 127 procedures in 89 controls.⁴⁹⁶ After 18 months, successful saphenous ablation was found in 92% of anticoagulated patients and in 95% of controls (p = .96). The frequency of DVT in the ipsilateral leg was low (1% in anticoagulated patients versus 1.6% in controls). Other smaller studies found similar results and a Delphi consensus also advised against bridging of vitamin K antagonists for endovenous ablation.¹²⁷ Anticoagulation treatment is not a contraindication to sclerotherapy.¹⁴³ However, patients should be advised that treatment success may be reduced and/or additional treatment sessions may be required.

Concerning treatment of deep vein pathology, anti-thrombotic regimens used in different studies are heterogeneous.³⁵⁵ Neither type of anticoagulation nor duration have been studied. In general, the advice is that patients on anticoagulants should not pause but switch to LMWH pre-operatively and continue this treatment shortly after the intervention (see subsection 5.3.4).

8.2.4. Elderly patients and patients with comorbidities

Epidemiological data from a large study on 38 750 US patients suggest that up to 30% of CVD presentations are in patients aged > 65 years.⁴⁹⁷ Commonly reported comorbidities in this cohort include diabetes (25%), hypertension (64%), chronic obstructive pulmonary disease (5%), history of cancer (12%), and stroke (3%). Coronary artery disease (0.12%) and peripheral artery disease (0.03%) are infrequent. Importantly those aged > 65 years are more likely to require venous intervention than their younger counterparts, given their higher rates of reported venous symptoms, as well as skin changes (12% vs. 6%, p < .001) and VLU (5% vs. 2%, p < .001).⁴⁹⁷

A multicentre prospective study confirmed comparable rates of efficacy and safety for EVTA in local tumescent anaesthesia in cohorts of patients aged > 75 years, with more comorbidities compared with younger patients.⁴⁹⁸ However, age was found to be a statistically significant risk factor for recanalisation in another study in elderly patients with an OR of 1.03 (95% CI 1.01 – 1.04, p < .001), which remained statistically significant in multivariable analysis.¹⁶⁵

Patients with right heart failure or tricuspid valve regurgitation may sometimes present with pulsatile VVs from high pressure reflux. In these patients, standard endovenous treatment modalities might fail as a result of insufficient inflammation and collapse of the treated vein. Pulsatile VVs are an indication for pre-operative cardiac evaluation, but information on this is scarce.

8.2.5. Children with chronic venous disease

In children CVD is rare and may be a result of congenital venous malformation (including atresia of deep veins), primary superficial and/or deep vein valve incompetence, or extensive DVT with secondary DVI and/or obstruction. Incidence of DVT and VTE has been increasing during the last decades because of more frequent use of central venous catheters in critically ill paediatric patients.² This has resulted in a rising incidence of paediatric PTS as, according to a meta-analysis, PTS occurs in 26% (0 – 77%) of paediatric DVTs.⁴⁹⁹

Management of children with CVD is mainly conservative, although venous interventions may be considered in highly symptomatic cases. EVLA has been reported feasible and safe in a small group of 35 children, with a median age of 14 years, undergoing EVLA mainly for venous malformations, Klippel-Trenaunay syndrome, and superficial venous reflux with VVs. The treatment was deemed successful in 83% of cases.⁵⁰⁰