The ESCHAR Trial: Should It Change Practice?

David D. I. Wright, MB, BSc, FRCS

Introduction: Most leg ulcers are caused by venous disease, the most common cause of venous hypertension being superficial vein incompetence. The ESCHAR trial tested the value of superficial vein surgery combined with compression in the healing and recurrence of venous leg ulcers compared with compression alone. Methods: A total of 500 patients with chronic venous leg ulcers, or recently healed ulcers, were randomized to superficial vein surgery and compression or compression alone. Vein surgery was saphenofemoral ligation and great saphenous stripping and phlebectomy or saphenopopliteal ligation and phlebectomy.

Perspectives in Vascular Surgery and Endovascular Therapy Volume 21 Number 2 June 2009 69-72 2009 The Author(s) 10.1177/1531003509337156 http://pvs.sagepub.com

Results: Ulcer healing was virtually identical between the 2 groups at 65% at 24 weeks; subgroup analysis failed to show a benefit for surgery to promote ulcer healing. Ulcer recurrence rate was halved in those that underwent surgery regardless of the presence of deep vein incompetence. Conclusion: Superficial vein surgery should be considered in all leg ulcer sufferers to reduce ulcer recurrence rather than accelerate ulcer healing. Keywords: ESCHAR trial; superficial vein surgery; leg ulcer

enous disease has been neglected, seen as unimportant medical condition, rarely is it life threatening and it is frequently considered only of cosmetic importance. The reality is very different, approximately 1% of the adult population have leg ulcer of venous origin at any one time and 4% are at risk of leg ulcer. Mean life time with leg ulcer is between 5 and 10 years at a cost of $6563 per leg per year, in total consuming in excess of 1% of the health care budget.1,2 Few patients receive definitive treatment for their leg ulcer and the general understanding was that these ulcers derived from the injury to deep veins following deep vein thrombosis and so there was no treatment available. With the advent of duplex ultrasound in the mid1980s, systematic noninvasive investigation of the venous system revealed that the majority of leg ulcer patients, although elderly, had simple superficial vein disease,3,4 and this finding has been repeated by many authors in different countries.
From BTG International Limited, London, United Kingdom. Address correspondence to: David D. I. Wright, BTG International Limited, 5 Fleet Place, London EC4M 7RD, United Kingdom; e-mail: david.wright@btgplc.com.

It is therefore an appealing notion that correction of superficial vein incompetence will correct the excess venous pressure and result in ulcer healing. However, in a number of studies the benefit of early ulcer healing has not been shown.5,6 The other important feature of leg ulcers is repeated recurrence; typically, over time the ulcerfree period declines and recurrent ulcers become harder to heal. Preventing recurrence is at least as important an objective as healing the ulcer. Reduction in ulcer recurrence has been shown to be significantly reduced from 38% to 9% at 3 years by the addition of superficial vein surgery.6 The standard of care for leg ulcer of venous origin is compression and various techniques including multilayer bandaging have proven highly effective with initial ulcer healing rates in excess of 70% at 6 months7,8 but subsequently a quarter of these ulcers recur by 1 year.9,10 The ESCHAR trial sought to assess the effect of superficial vein surgery and compression bandaging on ulcer healing and ulcer recurrence. This was a multicenter trial with patients with superficial vein incompetence, randomized equally to superficial vein surgery and compression or compression alone. The
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results of this study are presented in a number of publications.11-14

Patients
Consecutive patients referred with leg ulcer to vascular surgical services were assessed. Of 1418 screened for inclusion the major exclusions were presence of concomitant arterial disease (276, 20%), absence of reflux (211, 15%), and deep reflux only (59, 4%). A further 256 (33%) eligible patients refused consent unwilling to undergo surgery and were therefore excluded, 500 (35%) were randomized.

Surgery
Surgery in this study was saphenofemoral flush ligation and disconnection with stripping of the great saphenous vein to the knee and phlebectomy of varicosities or saphenopopliteal disconnection and phlebectomy. For those unfit for general anesthesia, saphenofemoral or saphenopopliteal disconnection was offered under local anesthesia. No specific surgery for perforating veins was provided, although it was noted that some perforators may have been avulsed with the phlebectomies.

Compression
Compression was provided by 4-layer compression bandage (Smith & Nephew, London, UK).

Results
The results are definitive, and with regard to ulcer healing, the 2 groups were virtually identical, with 65% healed in both groups at 24 weeks. Subgroup analysis of superficial reflux only, superficial and segmental deep reflux and superficial and total deep reflux again showed no benefit in favor of the surgery group towards healing. It seems clear that on the basis of these data and other studies that there is no indication for early superficial vein surgery to heal leg ulcers.11 Incompetent perforators were present in 59/115 (51%) legs before surgery and without specific perforator surgery this reduced to 44/104 (42%) at 12 months. The reduction in presence of incompetent

perforators was statistically significant in only the group with superficial reflux only, new perforators developed 12% of legs in the surgery group at 12 months.12 Ulcer recurrence was significantly reduced for all patients allocated to superficial vein surgery, reducing leg ulcer recurrence to 31% compared with 56% at 4 years. This study further supports the addition of superficial vein surgery regardless of the presence or absence of deep vein reflux. Superficial reflux alone or superficial with segmental deep recurrence rates were 27% and 24%, respectively, at 4 years compared with 51% and 52% for compression only. Surprisingly, the result for superficial and total deep reflux group was similar with 24% compared to with 46% at 3 years but this failed to reach significance due in part to small numbers, 9 and 7, respectively for surgery plus compression and compression only.14 The authors concluded that 85% of patients with chronic venous ulceration would benefit from surgery and should undergo venous duplex imaging with this in mind. The study results are not disputed, however, a number of factors minimized the measured benefit of surgery. The analysis was on the principle of intention to treat, in the surgical arm 19% did not receive surgery, and of those who did, many did not have reflux eliminated. For isolated superficial reflux only 7 of 63 had no reflux at 1 year and 25 had above-knee great saphenous vein incompetence. A similar picture is seen in the group with segment deep vein reflux.13 Surgery was delayed for an average of 7 weeks out of the 24-week ulcer-healing phase of the study. Although these factors may not have influenced the ulcer healing conclusion, as high-quality compression may have been the dominant therapy affecting healing, the benefit in ulcer recurrence may have been underestimated.

Should the Trial Results Change Practice?

The answer is simple, Yes, if the provision of venous duplex ultrasound imaging is not provided for all leg ulcer patients then practice should be changed to accommodate this increased level of investigation. If correction of superficial vein reflux is not offered to all those with superficial vein incompetence and ulcer, with the exception of those without

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axial superficial vein reflux and those with deep vein obstruction, then practice should be changed to permit access to treatment.

before the endorsement of heat ablation in the presence of an open ulcer.

Timing of Intervention
In the past, a widely held view was that superficial vein surgery should be deferred until the leg ulcer had healed, unfortunately as soon as an ulcer is healed, it is at risk of reulceration with average healing rates of 12 weeks a single avoidable recurrence is costly. On a more practical note ulcer patients are usually elderly and while the ulcer is open they may be happy to submit to intervention but once the ulcer is healed they are more likely to decline, with the inevitable ongoing risk of recurrence. Delay of surgical intervention was principally defended on the grounds of increased risk of wound infection. In the ESCHAR study of 242 patients treated surgically, only 5 had wound infection (2%) and only 1 required admission. On the basis of these data it can be concluded that intervention both investigative and corrective should be programmed into a patients management to take place in conjunction with the provision of compression and prior to ulcer healing.

Conclusions
The ESCHAR study is a well-designed and wellconducted study, which provides clear conclusions that should be incorporated into modern venous practice, namely duplex venous investigation and the offer of intervention where appropriate to all leg ulcer sufferers. The principal benefit is derived from a halving the ulcer recurrence rate, this result being confirmed in a systematic review.15 This study was conducted between 1999 and 2002 and published in 2004. Venous practice in the United States has during this period moved away from surgery to endovenous techniques. The same benefits can be anticipated from heat ablation of the superficial veins but this has yet to be demonstrated, a study similar to ESCHAR should be conducted for one or more of the heat ablation techniques.

References
1. Harrison MB, Graham ID, Lorimer K, Friedberg E, Pierscianowski T, Brandys T. Leg-ulcer care in the community before and after the implementation of an evidence-based service. CMAJ. 2005;172:1447-1452. 2. Nelzen O. Leg ulcers: economic aspects. Phlebology. 2000;15:110-114. 3. Grabs AJ, Wakely MC, Nyamekye I, Ghauri AS, Poskitt KR. Colour duplex ultrasonography in the rational management of chronic venous leg ulcers. Br J Surg. 1996;83:1380-1382. 4. Labropoulos N. Clinical correlation to various patterns of reflux. J Vasc Surg. 1997;31:242-247. 5. Guest M, Smith JJ, Tripuraneni G, et al. Randomised clinical trial of varicose vein surgery with compression versus compression alone for the treatment of venous ulceration Phlebology. 2003;18:130-136. 6. Zamboni P, Cisno C, Marchetti F, et al. Minimally invasive surgical management of primary venous ulcers vs. compression treatment: a randomised controlled trial. Eur J Vasc Endovasc Surg. 2003;26:337-338. 7. Blair SD, Wright DDI, Backhouse CM, Riddle E, McCollum CN. Sustained compression and healing of chronic venous ulcers. BMJ. 1989;297:159-161. 8. Moffatt CJ, Franks PJ, Oldroyd M, et al. Community clinics for leg ulcers and impact on healing. BMJ. 1992;305:1389-1392. 9. Wright DD, Franks PJ, Blair SD, Backhouse CM, Moffatt CJ, McCollum CN. Oxeruterins in the prevention of

Benefit of These Changes

The principal benefit derived from investigation and provision of treatment to eliminate superficial vein reflux is largely by way of reduced ulcer recurrence, which, if universally implemented, could reduce the ulcer population by a third or 600000 ulcer sufferers in the United States. Of course, much greater benefits could be obtained by addressing the at-risk populations of advance chronic venous insufficiency and healed leg ulcer CEAP C4 and C5.

Interpretation in the United States in 2009

It is widely believed that endovenous heat ablation whether by laser or radiofrequency results in a similar hemodynamic outcome to that of high ligation and saphenous stripping; however, the utility of heat ablation has yet to be demonstrated in leg ulcer. Beneficially, the level of invasion is reduced by endovenous ablation and therefore patient acceptability of intervention should be greater. Complications, principally infection, would also have to be evaluated

72 Perspectives in Vascular Surgery and Endovascular Therapy / Vol. 21, No. 2, June 2009 recurrence in chronic venous ulceration: randomised controlled trial. Br J Surg. 1991;78:1269-1270. 10. Franks PJ, Oldroyd M, Dickson D, Sharp E, Moffatt C. Risk factors for leg ulcer recurrence: a randomised controlled trial of two type of compression stocking. Age Ageing. 1995;240:490-494. 11. Barwell JR, Davies CE, Deacon J, et al. Comparison of surgery compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet. 2004;363:1854-1859. 12. Gohel MS, Barwell JR, Wakely C, et al. The influence of superficial venous surgery and compression on incompetent calf perforators in chronic venous leg ulceration. Eur J Vasc Endovasc Surg. 2005;29:78-82. 13. Gohel MS, Barwell JR, Earnshaw JJ, et al. Randomised clinical trial of compression plus surgery versus compression alone in chronic venous ulceration (ESCHAR study)haemodynamic and anatomical changes. Br J Surg. 2005;92:291-297. 14. Gohel MS, Barwell JR, Taylor M, et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ. 2007; 355:83-87. 15. Howard DP, Howard A, Kothari A, Wales L, Guest M, Davies AH. The role of superficial venous surgery in the management of venous ulcers: a systematic review. Eur J Vasc Endovasc Surg. 2008;36:458-465.

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