Standard, Appropriate, and Advanced Care and Medical-Legal Considerations: Part Two -- Venous Ulcerations

William J. Ennis, DO, MBA, FACOS, Patricio Meneses, PhD


Wounds. 2003;15(4) 

In This Article

Medical Therapy

Published rates of healing for venous ulcers utilizing moist wound healing and compression are frequently less than 65 percent at 24 weeks; therefore, many clinicians and researchers have sought adjunctive therapeutic alternatives. Systemic medical therapy presents an attractive potential option. As previously reviewed, there are numerous biochemical processes involved in venous ulcer formation, which are, theoretically, modifiable through systemic therapy. Pharmacologic therapy may be beneficial in modifying the microcirculatory changes that are secondary to raised ambulatory venous pressures.[124] It must be emphasized that medical therapy for venous ulcers is currently adjunctive to good local wound care and compression bandaging. A brief review of the published literature concerning the systemic treatment for venous ulcers follows.

Theoretically, fibrinolytic therapy should breakdown pericapillary fibrin. A group of compounds known as defibrotides, which have antithrombotic and fibrinolytic activity, have been studied.[125] Stanozolol, an anabolic steroid with fibrinolytic activity, has been shown to decrease lipodermatosclerotic skin changes but has not shown a benefit in ulcer healing.[126,127,128]

These agents are thought to restore endothelial barrier function. The clinical result has been reduction in both edema and symptoms of chronic venous insufficiency.[129,130,131] Recently, renewed interest in horse chestnut seed extract has resulted in over-the-counter health preparations touting edema control through similar mechanisms as the hydroxyrutosides.[132]

Prostaglandin E (PGE) has properties of vasodilation and inhibition of both platelet aggregation and polymorphonuclear cell activation. The majority of studies in the literature with this compound have been on arterial disease. One trial with intravenous PGE demonstrated promising results in the treatment of recalcitrant venous leg ulcers.[133]

Ifetroban, a thromboxane receptor antagonist, failed to show benefit over compression therapy in a randomized, controlled trial.[23] A daily regimen of oral aspirin resulted in a statistically significant improvement in venous ulcer healing in a randomized, controlled trial. There were only 20 patients and the control group demonstrated a zero-percent healing rate.[134] Clinical confirmation of this trial is needed, as this type of therapy would be very easy to implement.

The most extensively studied agent for the treatment of venous disease is pentoxifylline. The drug has mild fibrinolytic activity and an ability to decrease white blood cell aggregation. These properties are not as well known to the medical community where the red blood cell deforming properties are emphasized for the treatment of intermittent claudication.[2] Early reports demonstrated improvement in venous ulcer healing.[135,136] Dale, et al., found no significance with 400mg three times a day versus control in a 200-patient trial.[137] Recently, Falanga, et al., have demonstrated significantly faster healing rates by utilizing 800mg three times a day versus placebo or a standard regimen of 400mg three times a day.[138] Further trials with varying dosing regimens are obviously needed before final recommendations can be made.

In conclusion, systemic medical therapy for venous ulcers should be considered adjunctive therapy. All patients should be treated with compression and appropriate local care prior to considering systemic therapy. In cases where patients fail to improve and underlying microcirculatory issues are thought to be causative the clinician should consider these therapies for his or her recalcitrant patients.