Towards an evidenced package of care for venous ulceration

Venous ulceration remains a common problem, placing a heavy burden on both the affected individual and associated health services: an unhealed ulcer is estimated to cost approximately £1300 a year to treat. ¹ Attempting to reduce the cost of venous ulceration is logical at a time when funding in health care is coming under closer scrutiny, and would of course have significant health and quality-of-life gains. Improved efficiency in ulcer treatment may be achieved by adopting an evidence-based approach to build a complete package of care, instead of simply focusing on compression. The largest costs are accrued in the dressing of ulcers although the evidence for the use of expensive dressings is lacking. ² A Cochrane review of different dressing types did not identify any dressing as being more effective than a simple low-adherent dressing. ³ The VULCAN trial also failed to show any benefit for the routine use of silver donating antimicrobial dressings with regard to both ulcer healing and cost. ⁴

There is general agreement about the importance of compression therapy as the mainstay of treatment for venous ulcers: compression of any type is proven to be better than no compression. ^5,6 Four-layer bandaging systems are more effective in promoting ulcer healing than short-stretch bandaging. ⁷ Multilayer systems with elastic components are more effective in healing ulcers than those with inelastic components. ⁵ Intermittent compression can be used in those unable to tolerate continuous compression, or as an adjunct to formal compression bandaging. ⁶ When patients have problems with the application of bandages, adjustable compression boots can be used, and in small trials have been found to be as effective as compression bandaging. ⁵   Yet, there are a number of additional measures that could be added to compression that both improve ulcer healing and prevent future recurrence; the latter is an important component of the costs of care, and most existing research has focused on prevention of ulcer recurrence.

Ablation of superficial incompetence has the potential to make the biggest difference in the long term. It is therefore important in patients with ulceration to establish if there is any evidence of incompetence as a first step, with referral to a vascular surgeon if appropriate. Initially it was thought that surgical ablation of varicose veins could help speed healing of venous ulcers. In the Effect of Surgery and Compression on Healing and Recurrence (ESCHAR) Study, the largest trial of superficial venous surgery compared with compression alone, there was a significant decrease in ulcer recurrence (from 28% to 12% at 12 months after surgery), but no difference in the rate of ulcer healing. ⁸ Four-year follow-up continued to show a benefit for surgery in preventing ulcer recurrence (31% versus 56%). ⁹ Systematic review of all the superficial venous surgery trials produced similar results, with an overall ulcer healing rate of 81% (range 40–100%) and an ulcer recurrence rate of 15% (range 0–55%). ¹⁰ The addition of subfascial endoscopic perforator surgery has not been shown to impact on the outcome of surgery for patients with ulcers. ¹¹ Thus, ablation of superficial truncal incompetence has become an integral part of leg ulcer care, although with greater impact in the long term rather than the short term. There exist a number of novel endovenous methods of superficial vein ablation, and there is no logical reason to suppose that their use will not have a similar effect to superficial venous surgery. ¹² The main advantage of all modern therapies is that they can be done under local anaesthetic and in outpatients, thus avoiding the need for general anaesthesia and inpatient care.

Endovenous radio-frequency ablation is an alternative to surgery and has been shown to produce good ulcer healing rates (84% at 6 months) and low recurrence rates. ¹³ Similarly, endovenous laser ablation (EVLA) has been shown in one randomized trial to confer a healing advantage for venous ulcers. At 12 months, 24% (6/25) of patients undergoing compression alone had a healed ulcer compared with 81.5% (22/27) of patients undergoing EVLA and compression. ¹⁴ Ultrasound-guided foam sclerotherapy (UGFS) is another modern method of obliterating truncal venous incompetence. It has been shown to heal 96% (27/28) of ulcers at three months with a 7% recurrence rate at 12 months in a preliminary study. ¹⁵ It has the advantage of being associated with less pain, less analgesia, shorter time off work and a quicker return to driving compared with traditional surgery. ¹⁶ When the aforementioned study was expanded prospectively, the healing rate in 82 patients with active ulceration was 82% after a median of one month and the recurrence rate in 116 patients with C5/6 disease was 4.9% after two years. ¹⁷

It was hypothesized that as well as minimizing recurrence, foam sclerotherapy might actually improve healing rates, since it could be introduced into the ulcer pathway much earlier than the other therapies. There has been one randomized trial of UGFS in venous ulceration that failed to recruit enough patients to establish a difference in healing rates. It did show that it was feasible to include UGFS, and that it was a well-tolerated intervention. ¹⁸

Some widely available medications have been shown to influence ulcer healing. Pentoxifylline improves healing of venous ulcers both with, and without compression, with a number needed to treat between 7 and 11. ^19,20 It works by increasing red cell deformability, reducing plasma viscosity, decreasing platelet aggregation potential and hence reducing thrombus formation. ²¹ The majority of adverse effects from pentoxifylline are gastrointestinal in nature and most are tolerated by patients. ¹⁹ The addition of micronized purified flavonoid fraction (Daflon^®) to compression therapy is associated with a shorter time to ulcer healing and a better chance of ulcer healing;  the greatest benefit is for ulcers between 5 and 10 cm² in size and in those present for between six and 12 months. ²¹ The reduced healing time with pentoxifylline corresponds to a cost per quality-adjusted life years of greater than £125,000, so it seems this treatment should be reserved for a few selected patients ²² whereas Daflon has been shown to be cost-effective and this should be considered for more patients. ²³

Reducing the impact of venous ulceration through efficient, cost-effective treatment and the prevention of recurrence should be a priority. Unlike other high-cost, high-morbidity conditions, little attention has been paid to leg ulcers in the way of national guidelines, or advice from the National Institute of Health and Clinical Excellence in the UK. Perhaps that is one reason why Daflon, which is a cost-effective adjuvant therapy, is so underutilized in the UK. A review of Daflon concluded that it should be considered for a greater number of patients ²⁴ but it remains an unlicensed medication in the UK. Compression remains central to the pathway of care but treatment of superficial venous reflux is an important part of preventing ulcer recurrence. With an increasing number of patients unfit for, or unwilling to consider open surgery, the use of outpatient local anaesthetic procedures such as endothermal ablation, or more practically, foam sclerotherapy, is ideal. Yet there are other, less researched measures such as physical therapy, pinch skin grafting, and most recently, ultrasound therapy ²⁵ that could potentially be added to the package of care should more evidence become available.  Expanding the package of care could actually reduce the overall cost of managing leg ulcers.