title: Cilostazol for peripheral arterial disease.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance.
  
  
  OBJECTIVE
  To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC.
  
  
  METHODS
  The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2006). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles.
  
  
  METHODS
  Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD.
  
  
  METHODS
  Two authors independently assessed trials for selection and all three authors independently extracted data.
  
  
  RESULTS
  Eight randomised controlled trials comparing cilostazol with placebo were included. The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1; 95% confidence interval (CI): 21.4 to 40.9) and 50 mg twice daily (WMD 41.3; 95% CI: -7.1 to 89.7) compared with placebo. Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7; 95% CI: -9.6 to 41.0) compared with those receiving placebo. One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo. There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo.
  
  
  CONCLUSIONS
  Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Dept of Cardiac, Thoracic and Vascular Surgery, 5 Lower Kent Ridge Road, Singapore, 119074. surrpa@nus.edu.sg
authors.forename: P
authors.initials: P
authors.lastname: Robless
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: G P
authors.initials: GP
authors.lastname: Stansby
mesh_terms: D000368:Aged; D000077407:Cilostazol; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000517:prevention & control; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016138:Walking
chemical_list: D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol