Pentoxifylline

Jull, Andrew, et al. The Lancet, 2002, 359(9317), 1550-1554.

This work analyzed several published random controlled trials to compare pentoxifylline plus compression therapy to other treatment options for venous leg ulcers. The results suggest that pentoxifylline has an added benefit to compression therapy for venous leg ulcers and may be effective in people who are not receiving compression therapy.
· Methods
Eight trials enrolled 547 adult participants for this study. The research examined five trials using pentoxifylline combined with compression therapy against placebo compression therapy in 445 participants plus three trials comparing pentoxifylline alone versus placebo alone in 102 participants. The main goal was to test if pentoxifylline helps treat venous leg ulcers better than a placebo both with and without compression therapy. Analyses were conducted following the intention-to-treat principle.
· Results
Pentoxifylline demonstrated greater efficacy than placebo in achieving complete healing or significant improvement of venous leg ulcers (relative risk 1.49, 95% CI 1.11-2.01). Additionally, pentoxifylline combined with compression proved more effective than placebo with compression in achieving complete healing (1.30, 1.10-1.54). Patients receiving pentoxifylline experienced no more adverse events compared to those on placebo (1.25, 0.87-1.80). The most common side effect reported was mild gastrointestinal disturbance, occurring in 43% of participants.

Broderick, Cathryn, et al. Cochrane Database of Systematic Reviews, 2020, 10.

As a peripheral arterial disease (PAD) symptom intermittent claudication (IC) results in considerable morbidity and mortality rates. As a treatment for IC pentoxifylline functions by decreasing blood viscosity while enhancing red blood cell flexibility and microcirculatory flow alongside tissue oxygen levels.
This work encompassed all double-blind, randomized controlled trials (RCTs) which tested pentoxifylline against placebo or other drug therapies in Fontaine stage II IC patients. The main results were as follows:
· Across 17 studies that measured pain-free walking distance (PFWD) or total walking distance (TWD) improvements with pentoxifylline compared to placebo the percentage improvements in PFWD varied between -33.8% to 73.9% while TWD improvements ranged between 1.2% to 155.9%. The majority of the studies indicated pentoxifylline led to better PFWD and TWD outcomes than placebo with all evidence being of low certainty.
· Pre-exercise ankle-brachial pressure index (ABI) was compared between pentoxifylline and placebo in five studies which revealed no significant difference. Overall, there was no evidence of benefit for ABI or quality of life (QoL) (moderate-quality evidence).
· The research involved seven studies where pentoxifylline was tested against flunarizine, aspirin, Ginkgo biloba extract, nifedipine hydrochloride, prostaglandin E1 or buflomedil and nifedipine but the available data were insufficient to draw meaningful conclusions.
· Ultimately, the authors note the lack of high-quality evidence that pentoxifylline has an effect on IC compared with placebo or other treatments. Given the substantial heterogeneity between studies, the role of pentoxifylline in people with Fontaine class II IC remains uncertain.