Venous leg ulcers usually are treated with compression, but about 30 percent of patients still have unhealed ulcers after a year of compression therapy. Jull and colleagues studied the effectiveness of a common adjuvant therapy, pentoxifylline, which is thought to correct microcirculatory disorders by lowering blood viscosity.
They searched multiple sources for trials and references concerning the efficacy of pentoxifylline in venous ulcer therapy. They also hand-searched journals and conference proceedings and contacted drug manufacturers for unpublished information. Trials were included in the meta-analysis if they had an objective outcome measure, such as proportion of ulcers healed, change in ulcer area, or some other measure of change. Two of the researchers independently assessed each trial for quality, and statistical tests were used to assess publication bias and heterogeneity between trials.
Eight trials involving 547 adult patients were identified. Five trials compared pentoxifylline plus compression with placebo plus compression. The remaining three trials compared pentoxifylline with a placebo without compression. In most trials, the end point was healing of all ulcers or of the largest ulcer. Overall, pentoxifylline was associated with healing or substantial improvement over the placebo (relative risk, 1.49). In the studies that used compression, patients who received pentoxifylline were 30 percent more likely to heal than those who received a placebo. When compression was not used, patients who received pentoxifylline were nearly 2.5 times more likely to heal than those in the placebo group.
The most frequent adverse effect was mild gastrointestinal upset, and 25 percent of patient withdrawals were attributed to side effects. Four trials lasted eight to 12 weeks, and four lasted approximately six months. The relative risk of healing was greater with the shorter studies, but the heterogeneity between studies complicated comparisons.
The authors conclude that pentoxifylline improves healing of venous ulcers, especially in combination with compression. However, they caution that the many differences between trials limit generalization of the results. Some studies had relatively few patients, and results were skewed by patients with prolonged healing because of comorbidities. Nevertheless, several studies indicate benefit, and one study reported significant cost savings when pentoxifylline was used as adjunctive therapy.