Pentoxifylline for intermittent claudication
Abstract
Background
Intermittent claudication (IC) is a symptom of peripheral arterial occlusive disease (PAD). It is associated with high morbidity and mortality. Pentoxifylline is one of many drugs used to treat IC. Pentoxifylline decreases blood viscosity, improves erythrocyte flexibility, and increases microcirculatory flow and tissue oxygen concentration.
Many studies have evaluated the efficacy of pentoxifylline in treating PAD but the results of these studies are very variable.
Objectives
To determine the efficacy of pentoxifylline in improving the walking capacity (that is pain‐free walking distance and the total (absolute, maximum) walking distance) of patients with stable intermittent claudication, Fontaine stage II.
Search methods
The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched January 2011) and CENTRAL (2011, Issue 1). In addition, we searched MEDLINE (Week 2 January 2011) and EMBASE (2011 Week 03). ClinicalTrials.gov and Current Controlled Trials were searched for ongoing or unpublished trials.
Selection criteria
All double blind, randomised controlled trials (RCTs) comparing pentoxifylline to placebo or any other pharmacological intervention in patients with IC Fontaine stage II.
Data collection and analysis
Included studies were assessed separately by two review authors. Data were matched and disagreements resolved by discussion. The quality of the studies was assessed using the Jadad score and the Cochrane risk of bias tool. Results relating to pain‐free walking distance (PFWD) and total walking distance (TWD) were collected. Studies were compared based on the duration and dose of pentoxifylline.
Main results
Twenty‐three studies with 2816 participants were included in this review. There was considerable heterogeneity between the included studies with regards to multiple variables including duration of treatment, dose of pentoxifylline, baseline walking distance and patient characteristics, and therefore pooled analysis was not possible. The quality of the included studies was generally low. There was very large variability in the reported findings between the individual studies. In a total of 17 studies which compared pentoxifylline with placebo, of which 14 reported TWD and 11 reported PFWD, the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and for PFWD the difference ranged from ‐33.8% to 73.9%. Testing for statistical significance of these results was generally not possible due to the lack of data. There was no statistically significant difference in ankle brachial pressure index (ABI) between the pentoxifylline and placebo groups. Pentoxifylline was generally well tolerated.
Authors' conclusions
Given the generally poor quality of the published studies and the large degree of heterogeneity in the interventions and the results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline is generally well tolerated.
Based on the totality of the available evidence, it is possible that pentoxifylline could have a place in the treatment of IC as a means of improving walking distance and as a complimentary treatment assuming all other essential measures such as lifestyle change, exercise and treatment for secondary prevention have been taken into account. However, the response to pentoxifylline should be assessed on an individual basis.
PICOs
Plain language summary
Pentoxifylline for intermittent claudication
Atherosclerosis or hardening of the arteries results in narrowing and blockages in the arteries and can reduce the blood supply to the legs causing peripheral arterial occlusive disease. Intermittent claudication (IC) is a cramp‐like pain felt in the leg muscles that is brought on by walking and relieved by standing still or resting. Pentoxifylline is a drug that is used to relieve IC and to improve people’s walking capacity. It decreases blood viscosity and improves red blood cell flexibility, increasing microcirculatory blood flow and the amount of oxygen in the tissues. This review looked at all available evidence from randomised controlled trials on the efficiency of pentoxifylline in the treatment of IC.
Twenty‐three trials with a total of 2816 participants were included. A majority of the included studies suggested a mild to moderate improvement in pain‐free walking distance and total walking distance for pentoxifylline over placebo (and other treatments, which included Ginkgo biloba, buflomedil, iloprost, nylidrin and aspirin). The statistical significance of the findings from the individual trials was unclear and there was large variability in the effect of pentoxifylline between the different studies. The ankle brachial pressure index was not improved with pentoxifylline. The most commonly reported side effects were gastrointestinal symptoms, mainly nausea, and the drug was well tolerated.
The duration of trials, the dose of pentoxifylline and the distances that participants could walk at the start of the trials varied. The quality of the included studies was generally low.
Given all these factors, the role of pentoxifylline in intermittent claudication remains uncertain, and although it may have some beneficial effect for improving the walking distance of patients with IC, the response to pentoxifylline should be assessed on an individual basis.
