Venous Ulcers: The Evidence for Intervention

Even with optimal treatment of venous ulcers, healing may be prolonged and/or ineffective, and recurrence rates remain quite high. How should wound care clinicians and vascular specialists collaborate with care planning? 

Venous ulceration represents the most advanced stage of chronic venous disease and is responsible for approximately 70% of all chronic leg ulcers.^1-3 These ulcers affect approximately 1% of the population and are responsible for significant morbidity, decreased quality of life, and economic costs. Advanced venous disease may result from primary degenerative disorders or may be secondary to a previous episode of deep vein thrombosis (DVT). Additionally, venous ulceration may arise from venous valvular incompetence (reflux) in the superficial, deep, or perforating veins; from venous obstruction; or from a combination of both. Regardless of the underlying etiology, the final consequence is venous hypertension resulting in activation of the microvascular endothelium; leukocyte activation, adhesion, and migration; and inflammation ultimately leading to skin changes and ulceration.

Compression bandages and comprehensive wound care are the cornerstones of effective ulcer treatment. Although effective in healing 80% of ulcers,⁴ the time required for wound healing is often prolonged, some ulcers remain refractory to conservative management, and rates of recurrent ulceration are unacceptably high. Furthermore, compression alone does not address underlying pathophysiology and long-term compliance is often poor. Several interventions have been developed that address underlying reflux and obstruction. Additionally, evidence supporting venous intervention to prevent recurrence and, to a lesser extent, to accelerate wound healing is accumulating. Early collaboration between wound care and venous specialists is essential for the optimal care of these patients. This article will discuss how such a collaborative effort can improve patient outcomes while ultimately reducing costs.  

INTERVENTION FOR VENOUS REFLUX

Although venous ulceration can result from isolated superficial incompetence, reflux in advanced venous disease frequently occurs in patterns involving combinations of the deep, superficial, and perforating systems. Although several procedures for the correction of deep venous reflux have been developed, the benefit of these procedures remains uncertain.⁵ The best evidence supports intervention for superficial venous reflux and, to a somewhat lesser extent, reflux in the perforating veins. The impact of saphenous stripping on ulcer healing and recurrence has been the most rigorously evaluated. 

The ESCHAR (Effect of Surgery and Compression on Healing and Recurrence) study⁶ randomized 500 patients to superficial venous surgery in addition to compression or to compression alone. Although 24-week ulcer healing rates were identical (65%) in both arms, major criticisms have been that 16% of patients randomized to surgery in the intent-to-treat analysis subsequently refused intervention and that, although the primary endpoint was ulcer healing at 24 weeks, intervention was delayed a mean of seven weeks (interquartile range 4-14) among those randomized to surgery.  Furthermore, one-quarter of patients randomized to surgery underwent only junctional ligation, without stripping, under local anesthesia due to medical comorbidities. Despite these limitations, surgery did significantly reduce recurrent ulceration from 28% to 12% (P < .0001) at 12 months⁶ and from 56% to 31% (P < .001) at four years.⁷ At three-year follow up, surgery also resulted in a significantly greater ulcer-free time (100 versus 85 weeks, P = .013) in comparison to compression alone. Notably, benefits were also seen in patients living with concurrent superficial and deep venous reflux. A systematic review including five randomized trials published since 2000 also found a benefit for superficial venous surgery in terms of ulcer recurrence, but not ulcer healing.² Although most well-designed trials have evaluated the efficacy of superficial venous stripping for venous ulceration, stripping has largely been replaced by a variety of less invasive endovenous treatments, including both thermal and nonthermal techniques. The benefits of stripping can likely be extrapolated to current techniques for elimination of saphenous reflux. These techniques have proven to be at least as effective as surgery for symptomatic varicose veins.⁸ Although no comparative trials have evaluated endovenous ablation in comparison to either compression bandages or surgical stripping, series have reported improved venous hemodynamics⁹ and favorable clinical results with respect to ulcer recurrence.^4,8 As for the superficial veins, a variety of techniques, including subfascial endoscopic perforator surgery (SEPS), direct ligation, thermal ablation, and ultrasound-guided sclerotherapy, have been developed for the ablation of pathologic perforating veins. A pathologic perforating vein is defined as a perforator > 3.5 mm in diameter, having a reflux duration > 500 msec, and located beneath an open or healed venous ulcer.¹⁰ Trials comparing SEPS, often in conjunction with superficial venous surgery, with compression bandaging have suggested a benefit only in healing large (> 2.5 cm²) and medial ulcers.¹¹ However, there may also be some role for perforator intervention when used selectively in ulcers not responding to standard wound care or superficial venous intervention. For example, among 110 venous ulcers (72 patients) failing a minimum of five weeks of compression and wound care, perforator ablation resulted in a significant improvement in healing rate.¹²

INTERVENTION FOR VENOUS OBSTRUCTION

Obstruction of the proximal venous segments (inferior vena cava and iliac veins) is associated with clinical manifestations including edema, venous claudication, and venous ulceration.  Obstruction may result from either compressive lesions of the iliac veins, most commonly of the left common iliac vein between the overlying right common iliac artery and the lumbar vertebra, or a previous episode of DVT. Endovascular stenting has now largely replaced surgery for the management of these lesions. Most of the evidence supporting the value of stenting comes from large case series rather than well-designed comparative trials.¹³ Most series have evaluated ulcers failing conservative management and have demonstrated improvement following intervention, rates of persistent ulcer healing ranging from 56-100%. Despite the limitations of the available data, there is a strong clinical impression of benefit in individual patients.

CONCLUSION

Compression bandages and wound care remain the cornerstones in the effective treatment of venous ulcers. However, even with optimal treatment, healing is often prolonged, some ulcers fail to heal, and recurrence rates after healing remain quite high. There is clearly a role for venous intervention in the management of these patients. Once identified, a variety of procedures are available to address underlying reflux and obstruction. The current interventional guidelines of the Society for Vascular Surgery and the American Venous Forum¹⁴ are summarized in the Table above. 

Despite significant limitations, the current data do not suggest that superficial venous intervention, when added to standard compression therapy, significantly improves ulcer healing. However, venous ulceration is a disease of recurrence and such intervention does consistently and significantly reduce the risk of recurrence by about 50%.^2,11  The data supporting perforator intervention for venous ulcers are less robust than for superficial venous intervention. However, pathologic perforator ablation may have a role when applied selectively in large ulcers, medial ulcers, and ulcers responding poorly to standard compression and wound care. Although most of the evidence is limited to case series, there does appear to be a benefit to stenting of iliac obstructive lesions in patients failing conservative ulcer management. Failure to respond to standard compression bandaging and wound care mandates some consideration of intervention. Furthermore, and perhaps most importantly, the high risk of recurrence requires that most patients be evaluated for possible intervention. Optimal care of these patients clearly requires a partnership between the wound care and venous specialist. 

Mark H. Meissner is professor of venous and lymphatic disorders in the division of vascular surgery at the University of Washington. He was named the initial holder of the Peter Gloviczki Professorship in Venous and Lymphatic Disorders at the university in July 2016. He may be reached via email at meissner@u.washington.edu.

References

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