Efficacy and Safety of Pentoxifylline for Venous Leg Ulcers: An Updated Meta-Analysis

The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy-pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers. We systematically searched multiple electronic databases PubMed, Web of Science, Embase, the Cochrane Library, the Cochrane Central Register of Controlled Trials, China Science and Technology Journal Database, WanFang Data, China National Knowledge Infrastructure, and the Chinese Biomedical Literature Database to identify eligible studies. Randomized clinical trials of pentoxifylline versus placebo treatment in patients with venous leg ulcers were considered for inclusion. The primary outcomes included ulcer healing rate and the incidence of adverse events after treatment. The secondary outcomes were the ulcer significant improvement (the ulcer size shrank by more than 60% after treatment) rate, mean duration of complete wound healing and changes in mean ulcer size. A meta-analysis and qualitative analysis were conducted to estimate endpoints. A total of 13 randomized clinical trials, including 921 individuals, were finally included. Compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, P < .001) and significant improvement rate (RR = 2.36, 95%CI 1.31 to 4.24, P = .004) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, P = .04) at the same time. Moreover, pentoxifylline also shortened mean duration of complete wound healing (P = .007) and shrank ulcer size (P = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively. However, the evidence is insufficient to prove the results due to moderate-certainty evidence. Large-scale, well-designed randomized clinical trials are warranted.