Antithrombotic treatment for peripheral arterial disease

Context: Patients with peripheral arterial disease (PAD) bear a substantial risk for vascular events in the coronary, cerebral and peripheral circulations. In addition, this disorder is associated with a systemic milieu characterised by ongoing platelet activation and heightened thrombogenesis. Objective: To determine the optimal antithrombotic prophylaxis for patients with PAD. Data sources: Using terms related to PAD and antithrombotic agents, we searched the following databases for relevant articles: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the National Institutes of Health Clinical Trials Database, Web of Science, and the International Pharmaceutical Abstracts Database (search dates: 1 January 1990 to 1 January 2007). Additional articles were identified from cardiovascular and vascular surgery conference proceedings, bibliographies of review articles, and personal files. Study selection: We focused on randomised trials, systematic reviews and consensus guidelines of antithrombotic therapies for PAD. Data extraction: Detailed study information was abstracted by each author working independently. Results: Multiple studies show that patients with PAD manifest platelet hyperaggregability, increased levels of soluble platelet activation markers, enhanced thrombin generation and altered fibrinolytic potential. Many of these markers predict subsequent cardiovascular events. Available randomised trials and meta-analyses show that most available antithrombotic agents prevent major cardiovascular events and death in patients with PAD, including aspirin, aspirin/dipyridamole, clopidogrel, ticlopidine, picotamide and oral anticoagulants. Conclusions: Although the most favourable risk-benefit profile, cost-effectiveness and overall evidence base supports aspirin in this setting, we provide scenarios in which alternatives to aspirin should be considered.