A systematic review and meta-analysis assessing the impact of pentoxifylline on the healing and recurrence of venous leg ulcers

Introduction: Venous leg ulcers (VLU) are the most severe manifestation of venous insufficiency and carry a poor prognosis because of delayed healing and recurrent ulceration. Pentoxifylline (PTX) is an example of a vasoactive medication that can be used alongside compression therapy to help improve ulcer healing rates. A previous review highlighted improved healing of VLU with PTX, although no analysis was made for complete ulcer healing and recurrence following treatment. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The EMBASE, MEDLINE and Cochrane databases were searched for all relevant English-language human studies between January 1980 and August 2023. Two independent authors screened and reviewed all articles for inclusion, performed data extraction and assessed methodological quality according to Cochrane's risk of bias tool. Primary outcomes included complete ulcer healing and recurrence rates in the ipsilateral limb. Results: Ten studies were eligible for analysis, of which nine were randomised trials and one was an observational cohort study. There were a total of 1,025 participants, with 515 having received PTX. In those receiving 1200 mg PTX, venous leg ulcers healed in 62% (315 participants). Compared to controls, PTX administration was associated with a significantly higher likelihood of complete ulcer healing (OR 2.56, 95% CI 1.97-3.32, p < .001). The rate and time of ulcer recurrence were not recorded in any of the studies included. Conclusion: The evidence demonstrates that PTX may have a significant beneficial impact on the rate of complete ulcer healing. Little evidence is currently present in the literature evaluating the recurrence rates of ulcers following PTX treatment. Large scale, high quality RCTs with an adequate follow-up period are needed to evaluate this and assess whether treatment with PTX shows a significant benefit in prevention of recurrence in venous ulcers.