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

This randomized clinical trial uses data from the Early Venous Reflux Ablation trial to evaluate the long-term clinical and cost benefits of combined early endovenous ablation and compression compared with compression therapy alone and deferred ablation for treating superficial venous reflux of the leg. Key PointsQuestionIn patients with venous leg ulceration and superficial reflux, what is the clinical and cost-effectiveness of early endovenous ablation of reflux? FindingsIn this 450-patient, multicenter, randomized clinical trial, early endovenous ablation with compression accelerated venous ulcer healing, reduced the overall incidence of ulcer recurrence, and was highly cost-effective compared with compression with deferred intervention. MeaningTo deliver clinical and cost benefits, leg ulcer care pathways should be revised to include early assessment and treatment of superficial venous reflux. ImportanceOne-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. ObjectiveTo evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration. Design, Setting, and ParticipantsBetween 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. InterventionsPatients 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 MeasuresThe primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness. ResultsThe 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 20000 ($26283) per quality-adjusted life year and 90.8% likely at a threshold of 35000 ($45995) per quality-adjusted life year. Conclusions and RelevanceEarly 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 RegistrationClinicalTrials.gov identifier: ISRCTN02335796