The Impact of Pentoxifylline on the Healing and Recurrence of Venous Leg Ulcers: A Systematic Review and Meta-analysis

Introduction, Objectives, and/or Purpose: Venous leg ulcers (VLU) are a more severe manifestation of chronic venous insufficiency (CVI) and carries with it a poorer prognosis because of delayed healing and recurrent ulceration associated with CVI. The established treatment of VLUs is compression therapy to assist with blood flow and support the veins within the effected leg, and whilst medical adjuncts can be used alongside compression therapy, studies demonstrating the benefits and safety of these medical adjuncts remain controversial at present. Pentoxifylline (PTX) is an example of a medication used in peripheral vascular disease to aid with blood flow and can be used alongside compression therapy to help improve healing rates of ulcers, as demonstrated by a systematic review evaluating randomised controlled trials (RCTs) by Jull et al. in 2012. Whilst this review highlights improved healing of VLU, no analysis was made for complete ulcer healing and recurrence following treatment or, to our knowledge, has been made since.

Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched EMBASE, MEDLINE and Cochrane for all relevant English-language human studies between January 1980 and March 2023. Two independent authors screened and reviewed all articles for inclusion and data extraction and assessed methodological quality according to Cochrane’s risk of bias tool. Any discrepancies were discussed until consensus was reached. Primary outcomes included complete ulcer healing and recurrence rates of the ipsilateral limb. The certainty of the evidence included was assessed using the GRADE criteria.

Results: Ten studies were eligible for analysis, of which nine were RCTS and one was an observational cohort study. There was a total of 1,025 participants, with 515 having received PTX. Of those receiving PTX, venous leg ulcers were healed in 62% (315 participants). When compared to those not receiving PTX, participants within the treatment group showed a higher likelihood of complete ulcer healing (OR 2.56, 95% CI 1.97-3.32). The rate and time of ulcer recurrence were not recorded in any of the studies included.

Conclusion(s): Our evidence demonstrates that PTX has a 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. Larger scale, high quality RCTs with an adequate follow-up period should be conducted to properly evaluate this and assess whether treatment with PTX shows a significant benefit to prevention of recurrence of venous ulcers.