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

The need for a National Service Framework for leg ulcers.

Leg ulcers are common and costly to treat, and the quality of care provided to patients with this condition varies widely across the UK. The introduction of specialized community-based leg ulcer clinics in Gloucestershire has been associated with increased ulcer healing rates and decreased rates of ulcer recurrence, but this model of care has not been widely replicated. One way of ending this 'postcode lottery' is to produce a National Service Framework for leg ulcers, with the aim of delivering high-quality evidence-based care via such clinics under the supervision of local consultant vascular surgeons. Existing National Service Frameworks cover a range of common conditions that are, like leg ulceration, associated with significant morbidity, disability and resource use. These documents aim to raise quality and decrease regional variations in health care across the National Health Service, and leg ulceration fulfils all the necessary criteria for inclusion in a National Service Framework. Centrally defined standards of care for patients with leg ulceration, and the reorganization and restructuring of local services to allow the accurate assessment and treatment of such patients are required. Without a National Service Framework to drive up the quality of care across the country, the treatment of patients with leg ulcers will remain suboptimal for the majority of those who suffer from this common and debilitating condition

Avoiding blood transfusion in surgical patients (including Jehovah’s Witnesses).

When treating Jehovah's Witnesses, the surgical team should carefully discuss the risks and clarify which products and treatments are available and might be acceptable to the patient. A range of multidisciplinary pre, peri and post-operative blood conservation strategies can be employed to reduce the need for transfusion and should be considered in the management of all surgical patients

Residual venous reflux after superficial venous surgery does not predict ulcer recurrence.

OBJECTIVE: The aim of this study was to investigate the importance of venous reflux in ulcer recurrence following saphenous surgery. METHODS: Ulcerated legs (CEAP 5 and 6) with saphenous reflux were treated with superficial venous surgery plus compression as part of a clinical trial. Patients unfit for general anaesthesia (GA) underwent limited surgery under local anaesthesia (LA). Reflux in superficial and deep segments and venous refill times (VRTs) were assessed before surgery and 3-12 months post-operatively using duplex and digital photoplethysmography respectively. RESULTS: Of 185 patients treated with surgery, 15 failed to heal and 26 did not have a follow-up duplex. Within 3 years, 25 of the remaining 144 patients (17%) developed ulcer recurrence. Using a Cox regression model, the presence of residual venous reflux and change in reflux pattern were not found to be risk factors for ulcer recurrence (p=ns). LA was used in 4/25 patients who recurred compared to 28/119 who did not (p=0.60; Chi-square test). For legs with recurrence, median VRT before surgery was 10.5s (range 5-29) compared to 11s (range 6-36) after surgery (p=0.097, Wilcoxon Signed Rank test). However, in legs without recurrence, median VRT increased from 10s (range 3-48) to 15s (range 4-48) after surgery (p&lt;0.001). CONCLUSION: Residual reflux following saphenous surgery is not the most important predictor of venous ulcer recurrence. Poor venous function as demonstrated by VRT may be a better predictor of recurrence in these patients

Effect of foam sclerotherapy on healing and long-term recurrence in chronic venous leg ulcers.

INTRODUCTION: The ESCHAR trial showed that superficial venous surgery and compression in chronic venous ulceration achieved a 24-week healing rate of 65% and 12-month recurrence rate of 12%. Foam sclerotherapy treatment is an alternative to surgery. The aim of this study is to assess the effect of foam sclerotherapy on ulcer healing and recurrence in chronic venous leg ulcers. METHODS: Chronic venous leg ulcers (CEAP [clinical, aetiological, anatomical and pathological elements] 5 and CEAP 6) with superficial venous reflux were treated between March 2006 and June 2011 with ultrasound-guided foam sclerotherapy and compression.Venous duplex was performed on all legs before and after treatment. Twenty-four-week ulcer healing and one- and four-year ulcer recurrence rates were calculated using Kaplan–Meier survival analysis. RESULTS: Two hundred legs (186 patients) with chronic venous ulcers (CEAP 5: n ¼ 163 and CEAP 6: n ¼ 37) were treated with foam sclerotherapy. Complete occlusion was achieved in 185/200 (92.5%) limbs, short segment occlusion in 14/200 (7%) limbs and one leg segment failed to occlude. One patient suffered an asymptomatic non-occlusive deep vein thrombosis (DVT) diagnosed on duplex scan at one week and one presented with an occlusive DVT three weeks following a normal scan at one week. One patient developed an asymptomatic occlusive DVT at two weeks following a non-occlusive DVT diagnosed on initial one-week scan. Eighteen patients were lost to follow-up (3 moved away and 15 died of unrelated causes). The 24-week healing rate was 71.1% and one- and four-year recurrence rates were 4.7% and 28.1%, respectively. CONCLUSION: Foam sclerotherapy is effective in abolition of superficial venous reflux and may contribute to similar ulcer healing and long-term recurrence rates to superficial venous surgery. Foam sclerotherapy is an attractive alternative to surgery in this group of patients

The incidence and characterization of deep vein thrombosis following ultrasound-guided foam sclerotherapy in 1000 legs with superficial venous reflux

Objective: The incidence of deep vein thrombosis (DVT) following ultrasound-guided foam sclerotherapy (UGFS) ranges from 0% to 5.7%. The aim of this study was to assess the incidence of DVT following UGFS in a single vascular center. Methods: Patients undergoing UGFS between December 2005 and September 2011 underwent quality control duplex imaging within 2 weeks of treatment. This was performed by an independent senior vascular technologist, and data were entered on a prospectively maintained database. Deep venous segments assessed included common femoral vein, femoral vein, above- and below-knee popliteal veins, gastrocnemius, and tibial veins. DVT when present was labeled as endovenous foam-induced thrombosis (EFIT) type 1 when thrombus was lining&lt;25% of the lumen of the deep vein; type 2 when thrombus extension was 25% to 50%; type 3 when thrombus extension was 50% to 99%; and type 4 when the deep vein was occluded. Results: A total of 1166 UGFS treatments were performed in 1000 legs (776 patients). Complete occlusion of the treated veins was seen in 84.5% of the legs after one session of treatment. Overall, 17 DVTs were detected (1.5%) with no DVTs detected in legs undergoing multiple treatments. Of the 17 episodes of DVT, 16 legs had DVT following treatment for truncal reflux (658 legs; 2.43%). Seven DVTs were EFIT type 1, two were type 2, two were type 3, and five were type 4. One DVT was seen in the gastrocnemius vein alone. Two of 1166 treatments (0.2%) resulted in a symptomatic DVT, bothof which were EFIT type 4. On regression analysis, therewas an increase in the risk of DVT when ≥10 mL of foamwas injected (odds ratio, 4.63; 95% confidence interval,1.44-14.9; P = .01). Conclusions: The incidence of duplex-detected DVT following foam sclerotherapy is low and may be associated with the injection of ≥10 mL of foam. © 2013 Society for Vascular Surgery