Leg ulcers are a significant source of morbidity and health care expenditures, particularly in elderly patients. Several trials have shown that local treatment with ambulatory compression dressings and bandages for several months resulted in failure to heal in 30 to 60 percent of patients. Because several effects of pentoxifylline could promote ulcer healing, Dale and colleagues conducted a randomized, double-blind controlled trial of this drug as adjunct therapy in the treatment of venous leg ulcers.

The authors studied patients who were referred to specialized hospital clinics for the treatment of venous ulcers. Eligible patients had ulcers of at least 1 cm in diameter for at least two months. These patients were free of diabetes, arterial disease or systemic conditions. Ulcer classification was confirmed by ultrasonography, with diagnostic testing to exclude other potential causes of ulceration. Patients were excluded from the study if they had a recent myocardial infarction, major hemorrhage or lumbar sympathectomy, or had conditions or were taking medications that could interfere with the study. In addition to local treatments that used specialized dressings, patients were randomly assigned to receive 400 mg of pentoxifylline three times per day or an identical placebo. Patients were followed until the ulcer healed or 24 weeks of treatment had been completed.

The 101 patients taking pentoxifylline were similar to the 99 patients receiving placebo in all major respects. Within 24 weeks, ulcers healed in 65 (64 percent) of the patients receiving pentoxifylline compared with 52 (53 percent) of the patients receiving placebo. This difference did not achieve statistical significance. During the first six weeks of treatment, 14 percent of the ulcers in each group healed. Later in the trial, healing rates improved in the group using pentoxifylline. Few adverse effects were attributed to treatment, and the two groups were similar in reported adverse effects.

The authors conclude that pentoxifylline had a modest, nonsignificant effect on the healing rates of venous ulcers. According to the authors, patient selection was the main reason for the differences between their findings and those of previous studies. Previous studies included patients with diabetes or were not restricted to venous ulcers.

editor's note: This carefully conducted study showed an approximately 11 percent improvement in ulcer healing in the treated group. This improvement occurred only after six weeks of therapy. While any advantage in treatment is welcome, the authors are rightly cautious in their conclusion that the drug made only a marginal difference in healing rates. Besides patient selection and monitoring, the difference between this study and studies that reported substantial benefit from pentoxifylline therapy is the topical treatments used in addition to the medications. This study was part of a multifaceted investigation of ulcer management. All patients were aggressively treated with specialized local dressings and wound care. This care probably enhanced the healing rates in the placebo group, making it unusually difficult to detect added benefit from drug treatment. The cornerstone of ulcer management must remain expert wound care and attention to the general health of the patient.—a.d.w.