Six Year Extension Study of Patients From a Randomised Clinical Trial Comparing Venefit, Radiofrequency Induced Thermal Therapy, and Endovenous Radiofrequency Ablation for Treatment of Incompetent Great Saphenous Veins.

OBJECTIVE: To compare long term outcomes after great saphenous vein (GSV) treatment with three radiofrequency (RF) thermal devices: Venefit (Closurefast), Radiofrequency Induced Thermal Therapy (RFITT), and Endovenous Radiofrequency (EVRF). DESIGN: A 72 month follow up of patients who were treated in the randomised 3RF study. METHODS: A total of 172 participants from the 3RF study were invited to take part in a single visit, long term, follow up study. Failure of GSV closure was assessed with duplex ultrasound (DUS) and constituted the primary outcome. Patients completed questionnaires for secondary outcomes: Aberdeen Varicose Vein Questionnaire (AVVQ), Euroqol 5D (EQ-5D), and patient reported varicose veins measured by counting vein occupying boxes in AVVQ question 1. RESULTS: Twenty-two patients (12%) had already been re-treated. Of the remainder, 13 (7%) could not be contacted, 20 (11%) declined invitation, and one did not consent. Therefore, 116 (64%) and 95 (53%) participants completed questionnaires and DUS, respectively. Failure of GSV closure on 72 month DUS was 16%, 21%, and 37% for Venefit, RFITT, and EVRF, respectively (p = .14), whilst outcomes for all failures were 14%, 17%, and 44% (p < .001) (Venefit vs. EVRF: p < .001; RFITT vs. EVRF: p < .001; and Venefit vs. RFITT: p = .63). There were no between group differences in AVVQ or EQ-5D scores. Rates of patient reported presence of any varicose veins were high for all groups (97%, 92%, and 97% after Venefit, RFITT, and EVRF, respectively; p = .48). The EVRF treated participants reported more extensive recurrence than the Venefit and RFITT participants (p = .008). CONCLUSION: Long term technical outcomes after RF ablation for GSV varicose veins were significantly better after Venefit and RFITT compared with EVRF treatment. However, quality of life scores showed no differences after 72 months. Rates of patient reporting any varicose veins were high for all treatments. CLINICALTRIALS: gov Identifier: NCT04720027.

FOVELASS: A Randomised Trial of Endovenous Laser Ablation Versus Polidocanol Foam for Small Saphenous Vein Incompetence.

OBJECTIVE: To compare the outcomes of ultrasound guided foam sclerotherapy (UGFS) and endovenous laser ablation (EVLA) to treat isolated small saphenous vein (SSV) incompetence in a multicentre randomised controlled study (RCT; ClinicalTrials.gov identifier: NCT05468450). METHODS: Patients aged ≥ 18 years undergoing isolated SSV treatment (reflux > 0.5 seconds) were randomised to UGFS or EVLA. Patients treated with UGFS were allowed one additional truncal treatment at six weeks. Tributary treatments (phlebectomy or sclerotherapy) were permitted after six months. Participants were assessed at eight days, six months, and one, two, and three years. The primary endpoint was the absence of SSV reflux (> 0.5 seconds). Secondary outcomes included clinical scores and quality of life (QoL) scores. All analyses were done by intention to treat. RESULTS: Of 1 522 screened patients, 161 were randomised to UGFS (n = 82) and EVLA (n = 79). Only 3% of patients who received UGFS had the second (allowed) treatment and 86% of patients completed the three year study. Forty-one and 19 tributary treatments (by sclerotherapy) were performed in 27 UGFS patients (33%) and 15 EVLA patients (19%), respectively. The complete absence of reflux at three years was significantly better after EVLA (86%) than after UGFS (56%) (odds ratio [OR] 5.36, 95% confidence interval [CI] 2.31 - 12.44; risk ratio 1.59, 95% CI 1.26 - 2.01). Two deep vein thromboses (DVTs; one femoropopliteal and one gastrocnemius) and one endovenous heat induced thrombosis occurred in the EVLA group. Seven DVTs were seen in the UGFS group, including two partial popliteal DVTs and five gastrocnemius vein thromboses (four asymptomatic and incidental on day 8 screening). At three years, there was no difference between groups for the following: rate of visible varices (p = .87), revised Venous Clinical Severity Score (p = .28), and QoL (p = .59). Patient satisfaction scores were high in both groups (median score: EVLA 97/100 and UGFS 93/100; p = .080). Symptoms were significantly improved in both groups. (p < .001) CONCLUSION: Technical success was better for EVLA than for UGFS three years after SSV treatment. This agrees with studies that have reported on these treatments in the great saphenous vein. However, improvements in clinical outcome were similar for both groups.

The recommended goal in the United Kingdom's National Institute for Health and Care Excellence Clinical Guideline 168 for immediate referral of patients with bleeding varicose veins is not being achieved.

OBJECTIVE: Published in July 2013, National Institute for Health and Care Excellence Clinical Guideline 168 (CG168) recommended that people with bleeding varicose veins be referred immediately to a vascular service. We have examined the impact of CG168 on referral practice for patients with bleeding varicose veins from primary to secondary care in a local National Health Service setting. METHODS: Referrals to a local vascular service in the 6 years before (group 1) and 6 years after (group 2) publication of CG168 were analyzed to assess patients' management after a bleed, with particular reference to a patient's initial presentation and delays in referral to the vascular service. This was done by retrospective electronic database and case note interrogation of patients presenting with bleeding varicose veins. Relevant data were collected onto an Excel spread sheet (Microsoft, Redmond, Wash) in relation to demographic information, comorbidities, clinical presentation, and treatment pathway. RESULTS: During the period studied, 73 patients presented with bleeding varicose veins. Their mean age was 66 years, and 56% were men. Their mean body mass index was 28 kg/m2. Of note, 33 patients (45%) initially self-treated before going to see their general practitioner; another 18 (25%) went to the emergency department. In 51 patients (70%), the underlying superficial disease involved the great saphenous vein, and most patients (73%) were treated with foam sclerotherapy with or without truncal thermal ablation; 45 patients (group 1) were treated in the 6 years before publication of CG168, and 28 patients, allowing 6 months for dissemination, were treated in the 6 years after CG168 publication (group 2). Mean time from index bleed to referral to the vascular service was faster after publication of CG168 (84 days before and 20 days after publication of CG168; P = .00842). Publication of CG168 was also associated with reduced mean bleed to intervention times (194 vs 60 days; P = .00097). CONCLUSIONS: Publication of UK National Institute for Health and Care Excellence guideline CG168 has been associated with a significant reduction in the delay to referral of patients presenting with bleeding varicose veins; however, the goal of immediate referral to a vascular service is not being met. CG168 is likely to have been a significant component of the factors that have led to the improvements seen thus far.

Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial.

Importance: One-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer-free time for participants who are treated with early endovenous ablation of lower extremity superficial reflux. Objective: To evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration. Design, Setting, and Participants: Between October 24, 2013, and September 27, 2016, the EVRA randomized clinical trial enrolled 450 participants (450 legs) with venous leg ulceration of less than 6 months' duration and superficial venous reflux. Initially, 6555 patients were assessed for eligibility, and 6105 were excluded for reasons including ulcer duration greater than 6 months, healed ulcer by the time of randomization, deep venous occlusive disease, and insufficient superficial venous reflux to warrant ablation therapy, among others. A total of 426 of 450 participants (94.7%) from the vascular surgery departments of 20 hospitals in the United Kingdom were included in the analysis for ulcer recurrence. Surgeons, participants, and follow-up assessors were not blinded to the treatment group. Data were analyzed from August 11 to November 4, 2019. Interventions: Patients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n = 224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n = 226). Endovenous modality and strategy were left to the preference of the treating clinical team. Main Outcomes and Measures: The primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness. Results: The early-intervention group consisted of 224 participants (mean [SD] age, 67.0 [15.5] years; 127 men [56.7%]; 206 White participants [92%]). The deferred-intervention group consisted of 226 participants (mean [SD] age, 68.9 [14.0] years; 120 men [53.1%]; 208 White participants [92%]). Of the 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least 1 recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the 2 groups (hazard ratio, 0.82; 95% CI, 0.57-1.17; P = .28). Ulcers recurred at a lower rate of 0.11 per person-year in the early-intervention group compared with 0.16 per person-year in the deferred-intervention group (incidence rate ratio, 0.658; 95% CI, 0.480-0.898; P = .003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio, 1.36; 95% CI, 1.12-1.64; P = .002). At 3 years, early intervention was 91.6% likely to be cost-effective at a willingness to pay of £20 000 ($26 283) per quality-adjusted life year and 90.8% likely at a threshold of £35 000 ($45 995) per quality-adjusted life year. Conclusions and Relevance: Early endovenous ablation of superficial venous reflux was highly likely to be cost-effective over a 3-year horizon compared with deferred intervention. Early intervention accelerated the healing of venous leg ulcers and reduced the overall incidence of ulcer recurrence. Trial Registration: ClinicalTrials.gov identifier: ISRCTN02335796.

A Randomised Controlled Trial Comparing Three Different Radiofrequency Technologies: Short-Term Results of the 3-RF Trial.

OBJECTIVE: To date there has been no comparison of outcomes of endovenous radiofrequency (RF) devices. The 3-RF trial is the first randomised controlled trial of three commercially available RF ablation technologies. METHODS: Patients were recruited [182/302 patients with great saphenous vein (GSV) incompetence] into a prospective double blind randomised trial of Venefit, radiofrequency induced thermal therapy (RFITT), and endovenous radiofrequency (EVRF). The primary outcome measure was GSV closure (total/partial/failed) at six months. Secondary outcome measures included ablation times, complications, pain scores, analgesia requirements, and quality of life (QoL) scores to 12 months. RESULTS: Patients treated [180: Venefit (57), RFITT (64), EVRF (59)] were matched for age, sex, and vein characteristics. At six months, complete GSV closure was significantly better after Venefit and RFITT treatment (100% and 98%, respectively) compared with EVRF treatment (79%, p < .001). Mean treatment time was significantly faster for RFITT than for Venefit and EVRF (p < .0001). Euroqol 5D (EQ5D) visual analogue score (VAS) did not differ between groups at any time point. The only difference between groups in EQ5D domain scores was for the pain/discomfort domain at two weeks when significantly fewer EVRF patients reported no problems compared with Venefit and RFITT. This difference had disappeared at six and 12 months. The Aberdeen Varicose Vein Questionnaire (AVVQ) improved for all groups at six and 12 months compared with pre-treatment levels; however, there was no significant difference between groups. CONCLUSION: Compared with Venefit and RFITT, EVRF was associated with significant failure of truncal ablation at six months; however, clinical outcomes did not differ significantly at 12 months. clinicaltrials.gov identifier: NCT02441881, NHS Health Research Authority (Hampstead Research Ethics Committee) number: 14/LO/1232.

Early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration: the EVRA RCT.

BACKGROUND: Venous ulceration is a common and costly health-care issue worldwide, with poor healing rates greatly affecting patient quality of life. Compression bandaging has been shown to improve healing rates and reduce recurrence, but does not address the underlying cause, which is often superficial venous reflux. Surgical correction of the reflux reduces ulcer recurrence; however, the effect of early endovenous ablation of superficial venous reflux on ulcer healing is unclear. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of compression therapy with early endovenous ablation of superficial venous reflux compared with compression therapy with deferred endovenous ablation in patients with venous ulceration. DESIGN: A pragmatic, two-arm, multicentre, parallel-group, open randomised controlled trial with a health economic evaluation. SETTING: Secondary care vascular centres in England. PARTICIPANTS: Patients aged ≥ 18 years with a venous leg ulcer of between 6 weeks' and 6 months' duration and an ankle-brachial pressure index of ≥ 0.8 who could tolerate compression and were deemed suitable for endovenous ablation of superficial venous reflux. INTERVENTIONS: Participants were randomised 1 : 1 to either early ablation (compression therapy and superficial endovenous ablation within 2 weeks of randomisation) or deferred ablation (compression therapy followed by endovenous ablation once the ulcer had healed). MAIN OUTCOME MEASURES: The primary outcome measure was time from randomisation to ulcer healing, confirmed by blinded assessment. Secondary outcomes included 24-week ulcer healing rates, ulcer-free time, clinical success (in addition to quality of life), costs and quality-adjusted life-years (QALYs). All analyses were performed on an intention-to-treat basis. RESULTS: A total of 450 participants were recruited (224 to early and 226 to deferred superficial endovenous ablation). Baseline characteristics were similar between the two groups. Time to ulcer healing was shorter in participants randomised to early superficial endovenous ablation than in those randomised to deferred ablation [hazard ratio 1.38, 95% confidence interval (CI) 1.13 to 1.68; p = 0.001]. Median time to ulcer healing was 56 (95% CI 49 to 66) days in the early ablation group and 82 (95% CI 69 to 92) days in the deferred ablation group. The ulcer healing rate at 24 weeks was 85.6% in the early ablation group, compared with 76.3% in the deferred ablation group. Median ulcer-free time was 306 [interquartile range (IQR) 240-328] days in the early ablation group and 278 (IQR 175-324) days in the deferred endovenous ablation group (p = 0.002). The most common complications of superficial endovenous ablation were pain and deep-vein thrombosis. Differences in repeated measures of Aberdeen Varicose Vein Questionnaire scores (p < 0.001), EuroQol-5 Dimensions index values (p = 0.03) and Short Form questionnaire-36 items body pain (p = 0.05) over the follow-up period were observed, in favour of early ablation. The mean difference in total costs between the early ablation and deferred ablation groups was £163 [standard error (SE) £318; p = 0.607]; however, there was a substantial and statistically significant gain in QALY over 1 year [mean difference between groups 0.041 (SE 0.017) QALYs; p = 0.017]. The incremental cost-effectiveness ratio of early ablation at 1 year was £3976 per QALY, with a high probability (89%) of being more cost-effective than deferred ablation at conventional UK decision-making thresholds (currently £20,000 per QALY). Sensitivity analyses using alternative statistical models give qualitatively similar results. LIMITATIONS: Only 7% of screened patients were recruited, treatment regimens varied significantly and technical success was assessed only in the early ablation group. CONCLUSIONS: Early endovenous ablation of superficial venous reflux, in addition to compression therapy and wound dressings, reduces the time to healing of venous leg ulcers, increases ulcer-free time and is highly likely to be cost-effective. FUTURE WORK: Longer-term follow-up is ongoing and will determine if early ablation will affect recurrence rates in the medium and long term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02335796. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 24. See the NIHR Journals Library website for further project information.

Venous leg ulcers are open wounds occurring on the legs of patients with venous disease. They are common, painful and distressing and reduce patient quality of life. Leg ulcers often result from valves in the leg veins not working properly. The valves normally force blood back up towards the heart; however, blood can flow backwards (reflux) when valves do not work properly, and this can cause swelling and ulceration. Compression therapy (wrapping bandages around the legs) has been shown to help ulcers heal, but it does not treat the underlying reflux problem with the veins. Newer, less invasive, techniques (known as endovenous ablation) have taken over from surgery to correct venous reflux and are more acceptable to patients as they can be performed quickly under local anaesthetic. The aim of the trial was to find out if treating patients with leg ulcers by early endovenous ablation (within 2 weeks) and standard compression therapy can increase ulcer healing compared with standard compression therapy and delayed endovenous ablation once the ulcer has healed. In total, 450 people agreed to take part in this study and were treated in 20 hospitals across England. Participants were randomly allocated to either early or delayed endovenous ablation and followed up for 12 months. The trial found that treating the veins early resulted in quicker ulcer healing than delaying treatment until the ulcer had healed. The trial also showed that participants had more time without an ulcer if the treatment was performed early rather than after ulcer healing. No safety issues with early intervention were identified. There is some evidence that quality of life was better in the early treatment group and that people in this group had less body pain. Treating ulcers early appears likely to be more cost-effective (i.e. a better use of NHS resources) than delayed treatment. Future work will focus on collecting longer-term follow-up data to find out if early endovenous ablation also reduces the chances of the ulcer coming back.

A practical approach to tumescent local anaesthesia in ambulatory endovenous thermal ablation.

BACKGROUND: Thermal ablation, usually performed with tumescent local anaesthesia (TLA), is the preferred method for varicose veins treatment. Tumescent local anaesthesia is always cited; however, little detail of the procedure is presented in publications. This retrospective audit of clinical tumescent local anaesthesia practice aims to provide detailed information on an important aspect of endovenous practice. METHODS: Patients who underwent three types of endothermal treatment (Venefit, Radiofrequency Induce Thermal Therapy and Endovenous Laser Ablation) to a single saphenous trunk using tumescent local anaesthesia were assessed. Differences in tumescent local anaesthesia volume per unit length of treated vein were assessed for the followings: type of saphenous trunk, length of vein treated, effect of additional phlebectomy and bilateral versus interval unilateral treatment for bilateral veins. Descriptive data are reported as mean and standard deviation, and groups were compared using the one-way ANOVA test. RESULTS: Between 2008 and 2014, single-saphenous-trunk ambulatory TLA thermal ablation was performed in 979 patients, mean age was 54 years. A total of 1229 limbs had truncal ablations and synchronous phlebectomy was performed in 470 limbs. No tumescent local anaesthesia-related complications occurred. There was no significant difference in standardised tumescent local anaesthesia volume per centimetre (ml) used for the three devices. Tumescent local anaesthesia volume per centimetre (ml) differed significantly between saphenous trunks. On average, a standard 10-12 ml/cm of tumescent local anaesthesia was used for saphenous trunks. Mean total tumescent local anaesthesia volume per patient, when treating the great saphenous vein alone, was 931 ml for bilateral and 425 ml for unilateral treatment. CONCLUSION: This report of over 1000 endovenous procedures demonstrates safe performance of laser and radiofrequency treatments using tumescent local anaesthesia. Although no attempt was made to determine minimum volume requirements, a mean tumescent local anaesthesia volume of 10-12 ml/cm administered to the perivenous space provides adequate anaesthesia for truncal saphenous ablation.

A Randomized Trial of Early Endovenous Ablation in Venous Ulceration.

BACKGROUND: Venous disease is the most common cause of leg ulceration. Although compression therapy improves venous ulcer healing, it does not treat the underlying causes of venous hypertension. Treatment of superficial venous reflux has been shown to reduce the rate of ulcer recurrence, but the effect of early endovenous ablation of superficial venous reflux on ulcer healing remains unclear. METHODS: In a trial conducted at 20 centers in the United Kingdom, we randomly assigned 450 patients with venous leg ulcers to receive compression therapy and undergo early endovenous ablation of superficial venous reflux within 2 weeks after randomization (early-intervention group) or to receive compression therapy alone, with consideration of endovenous ablation deferred until after the ulcer was healed or until 6 months after randomization if the ulcer was unhealed (deferred-intervention group). The primary outcome was the time to ulcer healing. Secondary outcomes were the rate of ulcer healing at 24 weeks, the rate of ulcer recurrence, the length of time free from ulcers (ulcer-free time) during the first year after randomization, and patient-reported health-related quality of life. RESULTS: Patient and clinical characteristics at baseline were similar in the two treatment groups. The time to ulcer healing was shorter in the early-intervention group than in the deferred-intervention group; more patients had healed ulcers with early intervention (hazard ratio for ulcer healing, 1.38; 95% confidence interval [CI], 1.13 to 1.68; P=0.001). The median time to ulcer healing was 56 days (95% CI, 49 to 66) in the early-intervention group and 82 days (95% CI, 69 to 92) in the deferred-intervention group. The rate of ulcer healing at 24 weeks was 85.6% in the early-intervention group and 76.3% in the deferred-intervention group. The median ulcer-free time during the first year after trial enrollment was 306 days (interquartile range, 240 to 328) in the early-intervention group and 278 days (interquartile range, 175 to 324) in the deferred-intervention group (P=0.002). The most common procedural complications of endovenous ablation were pain and deep-vein thrombosis. CONCLUSIONS: Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796 .).

Case report: Limb-threatening femoral vein thrombosis in a healthy carpet fitter: Carpet fitter's thrombosis.

OBJECTIVE: To report a case of femoral vein thrombosis in a carpet fitter and to highlight this as an occupational hazard. METHOD: Case presentation and literature review. RESULTS: An otherwise fit 21-year-old carpet fitter with no past medical history presented with acute thrombosis of his left common femoral, superficial femoral and great saphenous veins. Attempted catheter directed thrombolysis was unsuccessful. Due to severe pain and the threat of venous gangrene he was treated by emergency surgical thrombectomy with excision of chronic venous scarring and vein-patch repair that led to resolution of his symptoms. CONCLUSIONS: Deep vein thrombosis is typically associated with factors such as increasing age and prolonged periods of immobility; however, certain 'active' occupations can increase its risk. Crouched and cramped working conditions including repetitive active movement with flexed hips and knees can predispose to increased risk of venous thromboembolism.

Radiofrequency ablation of varicose veins: Best practice techniques and evidence.

SCOPE OF THE REVIEW: This article systematically reviews the practice of radiofrequency ablation of lower limb varicose veins. We present the clinical evidence and best practice techniques for currently available devices. METHODS: Manufacturer's instructions-for-use were requested for all radiofrequency devices. The MEDLINE and EMBASE databases were searched using the following keywords: 'varicose veins' AND 'radiofrequency' OR 'radio frequency' OR 'Venefit' OR 'ClosureFAST' OR 'RFiTT' OR 'EVRF' OR 'VeinCLEAR', generating 240 articles. Titles and abstracts were screened, yielding 63 articles directly relevant to the scope of the review. Reference lists for publications were also searched to identify further manuscripts of relevance. The Cochrane Database and current National Institute for Clinical and Healthcare Excellence guidelines for varicose veins were also searched from relevant articles. RESULTS: Four radiofrequency ablation (RFA) systems are currently commercially available. Generic practice methods (common to all RF systems) and device-specific techniques are described. The weight of current evidence relates to the use of Covidien Venefit™ (formerly VNUS ClosureFAST™), which clearly demonstrates clinical advantages over open surgery at least to 2 years follow up. However, contemporary studies of the radiofrequency-induced thermal therapy device (RFiTT®), show that in experienced hands, clinical equivalence to the Venefit™ procedure can be achieved. The evidence base for EVRF® and VeinCLEAR™ devices is currently weak and absent, respectively. CONCLUSIONS: Despite widespread uptake of RFA and acceptance of its clinical advantages over open surgery there is a paucity of Class 1 A evidence. This results from incongruent reporting of clinical outcome measures within existing literature. Similarly, lack of long-term follow-up studies precludes comparison of the durability of short- and medium-term advantages of RFA with the longer term results of open surgery. There remains scope for a large prospective high-quality trial to assess the clinical, anatomical and cost-effectiveness outcomes for the four commercially available RFA devices, with a particular focus on long-term follow up.