title: 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.
  
  
  OBJECTIVE
  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.
  
  
  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 ClinicalTrials.gov and Current Controlled Trials were searched for ongoing or unpublished trials.
  
  
  METHODS
  All double blind, randomised controlled trials (RCTs) comparing pentoxifylline to placebo or any other pharmacological intervention in patients with IC Fontaine stage II.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Harefield Heart Science Centre, National Heart and Lung Institute, Imperial College London,Harefield, Middelsex, UB9 6JH, UK. kareemsal@doctors.net.uk.
authors.forename: Kareem
authors.initials: K
authors.lastname: Salhiyyah
authors.forename: Eshan
authors.initials: E
authors.lastname: Senanayake
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdel-Hadi
authors.forename: Andrew
authors.initials: A
authors.lastname: Booth
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Michaels
mesh_terms: D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D010431:Pentoxifylline / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016138:Walking
chemical_list: D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D010431:Pentoxifylline