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Doctor examines the leg old female patient for varicose veins

NIHR Signal Varicose vein injections help new venous leg ulcers heal

Published on 18 July 2018

doi: 10.3310/signal-000622

For patients with leg ulcers caused by varicose veins, early intervention to treat the veins results in faster healing of ulcers than standard compression therapy alone.

Researchers studied 450 people with open venous leg ulcers of 6 weeks to 6 months duration and varicose veins. Those assigned to have their veins treated within two weeks had healed ulcers in an average of 56 days, compared with 82 days for those who had treatment deferred for six months, or until after the ulcer had healed.

In this NIHR-funded study, all patients were treated with compression therapy using bandages or stockings, administered by nursing staff. Most varicose vein treatment was carried out by foam sclerotherapy, where a solution is injected into the vein to close it, although the method could be chosen locally.

The study suggests early varicose vein treatment is beneficial. Current treatment guidance does not recommend any preferred timing of treatment.

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Why was this study needed?

Long-term venous leg ulcers are common, with overall population prevalence amongst all ages of about 0.1 to 0.3% in the UK. Prevalence increases with age, and about 1% of the population will suffer from leg ulceration at some point in their lives.

Between 60 to 85% of all leg ulcers are venous caused by varicose veins. Standard therapy includes cleaning, dressing the wound, and applying compression therapy. However, even with treatment in specialist clinics, only about 70% of small ulcers heal within six months and recurrence within a year is common. Some estimates suggest their treatment and management cost the NHS £1.94 billion a year.

Previous studies have shown that surgery to treat varicose veins may reduce ulcer recurrence. In 2009/10 there were 35,659 varicose veins procedures carried out in the NHS. Clear evidence about how early referral for varicose vein surgery affects ulcer healing has been lacking.

What did this study do?

Twenty treatment centres around the UK took part in the EVRA randomised controlled trial. The 450 participants were assigned to either compression therapy plus ablation of varicose veins within two weeks of randomisation, or standard compression therapy but with delayed consideration of intervention. The delayed decision was made after ulcer healing or six months after randomisation.

Patients were excluded if they were pregnant, unable to adhere to compression therapy, had deep vein disease, needed skin grafting, or had the ulcer for less than six weeks or more than six months. Many people were not eligible because the ulcer had been present for too long, more than six months, or had healed by the time of referral. Some declined due to clinician or personal preference for treatment, so these results may not apply to all people with varicose ulcers. 

What did it find?

  • The median time for the ulcer to heal among patients randomised to early treatment was 56 days (95% confidence interval [CI] 49 to 66), compared with 82 days (95% CI 69 to 92) for patients who had treatment deferred.
  • Ulcers healed by 24 weeks in 85.6% (95% CI 80.6 to 89.8%) of patients randomised to early treatment, compared to 76.3% (95% CI 70.5 to 81.7%) who had treatment deferred. Rates of ulcer healing were higher than is commonly reported in clinical practice.
  • Patients in the early-intervention group were more likely to have longer ulcer-free time than those in the deferred-intervention group (odds ratio of being in a higher quartile of ulcer-free time, 1.54, 95% CI 1.07 to 2.20).
  • There was no clear difference between the groups on quality of life measures.

What does current guidance say on this issue?

NICE guidelines published in 2013 say people with varicose veins should be referred to a vascular service if they have a venous leg ulcer that has not healed within two weeks. After assessment, suitable patients should be offered endothermal ablation (first line) or foam sclerotherapy.

Guidance in a NICE Clinical Knowledge Summary says management of venous leg ulcers includes cleaning, compression therapy, follow up and lifestyle advice. It says clinicians should “Consider referral to a specialist leg ulcer clinic or tissue viability clinic if available, or to a dermatology or vascular specialist, depending on clinical judgement.”

What are the implications?

Promptly referring all patients with a leg ulcer for varicose vein treatment might shorten time to healing, but cause expansion of demand for treatment. We cannot tell from this study whether ulcers that are persistent for over six months would respond as well, though recurrent ulcers were included in this study.

However, dressing leg ulcers is a time-consuming activity, and they are common. Earlier healing might reduce the resources spent on them.

Citation and Funding

Gohel MS, Heatley F, Liu X, et al.; EVRA Trial Investigators. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14.

This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 11/129/197).

Bibliography

NICE. Varicose veins: diagnosis and management. London: National Institute for Health and Care Excellence; 2013.

NICE. Clinical Knowledge Summary. Leg ulcer – venous. London: National Institute for Health and Care Excellence; 2016.

Why was this study needed?

Long-term venous leg ulcers are common, with overall population prevalence amongst all ages of about 0.1 to 0.3% in the UK. Prevalence increases with age, and about 1% of the population will suffer from leg ulceration at some point in their lives.

Between 60 to 85% of all leg ulcers are venous caused by varicose veins. Standard therapy includes cleaning, dressing the wound, and applying compression therapy. However, even with treatment in specialist clinics, only about 70% of small ulcers heal within six months and recurrence within a year is common. Some estimates suggest their treatment and management cost the NHS £1.94 billion a year.

Previous studies have shown that surgery to treat varicose veins may reduce ulcer recurrence. In 2009/10 there were 35,659 varicose veins procedures carried out in the NHS. Clear evidence about how early referral for varicose vein surgery affects ulcer healing has been lacking.

What did this study do?

Twenty treatment centres around the UK took part in the EVRA randomised controlled trial. The 450 participants were assigned to either compression therapy plus ablation of varicose veins within two weeks of randomisation, or standard compression therapy but with delayed consideration of intervention. The delayed decision was made after ulcer healing or six months after randomisation.

Patients were excluded if they were pregnant, unable to adhere to compression therapy, had deep vein disease, needed skin grafting, or had the ulcer for less than six weeks or more than six months. Many people were not eligible because the ulcer had been present for too long, more than six months, or had healed by the time of referral. Some declined due to clinician or personal preference for treatment, so these results may not apply to all people with varicose ulcers. 

What did it find?

  • The median time for the ulcer to heal among patients randomised to early treatment was 56 days (95% confidence interval [CI] 49 to 66), compared with 82 days (95% CI 69 to 92) for patients who had treatment deferred.
  • Ulcers healed by 24 weeks in 85.6% (95% CI 80.6 to 89.8%) of patients randomised to early treatment, compared to 76.3% (95% CI 70.5 to 81.7%) who had treatment deferred. Rates of ulcer healing were higher than is commonly reported in clinical practice.
  • Patients in the early-intervention group were more likely to have longer ulcer-free time than those in the deferred-intervention group (odds ratio of being in a higher quartile of ulcer-free time, 1.54, 95% CI 1.07 to 2.20).
  • There was no clear difference between the groups on quality of life measures.

What does current guidance say on this issue?

NICE guidelines published in 2013 say people with varicose veins should be referred to a vascular service if they have a venous leg ulcer that has not healed within two weeks. After assessment, suitable patients should be offered endothermal ablation (first line) or foam sclerotherapy.

Guidance in a NICE Clinical Knowledge Summary says management of venous leg ulcers includes cleaning, compression therapy, follow up and lifestyle advice. It says clinicians should “Consider referral to a specialist leg ulcer clinic or tissue viability clinic if available, or to a dermatology or vascular specialist, depending on clinical judgement.”

What are the implications?

Promptly referring all patients with a leg ulcer for varicose vein treatment might shorten time to healing, but cause expansion of demand for treatment. We cannot tell from this study whether ulcers that are persistent for over six months would respond as well, though recurrent ulcers were included in this study.

However, dressing leg ulcers is a time-consuming activity, and they are common. Earlier healing might reduce the resources spent on them.

Citation and Funding

Gohel MS, Heatley F, Liu X, et al.; EVRA Trial Investigators. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105-14.

This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 11/129/197).

Bibliography

NICE. Varicose veins: diagnosis and management. London: National Institute for Health and Care Excellence; 2013.

NICE. Clinical Knowledge Summary. Leg ulcer – venous. London: National Institute for Health and Care Excellence; 2016.

A randomized trial of early endovenous ablation in venous ulceration

Published on 26 April 2018

M Gohel, F Heatley, X Liu, A Bradbury, R Bulbulia, N Cullum, Epstein, I Nyamekye, K Poskitt, S Renton, J Warwick, A Davies

New England Journal of Medicine , 2018

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.)

Expert commentary

Venous ulceration has a huge impact on quality of life and healthcare resources. This study demonstrates a clear benefit in terms of time to healing and ulcer free time when veins are treated early by keyhole techniques and thereby provide sound evidence for clinicians and managers looking at how best to allocate scarce resources.

Interestingly, they screened 6,555 patients to be able to randomise just 450 patients to the study. This shows how complex the management of ulcers can be and perhaps underlines the wider issue of the need for integrated multidisciplinary services in the management of leg ulcers.

Harvey Chant, Consultant Vascular Surgeon, Royal Cornwall Hospitals