Clinical Question: Which antiplatelet agents, used alone or in combination, are effective in preventing recurrent vascular events?

Setting: Various (meta-analysis)

Study Design: Systematic review

Synopsis: Investigators rigorously searched multiple databases, including MEDLINE, the Cochrane Clinical Trials Registry, and reference lists of trials, review articles, and scientific statements and guidelines of official societies. Randomized trials comparing an antiplatelet regimen with placebo or another antiplatelet regimen and assessing outcomes for at least 10 days were included. The authors identified 111 trials that together enrolled nearly 100,000 patients. The investigators do not state whether the search for, and evaluation of, the included studies was done independently or by more than one person. No formal assessment of the potential for publication bias was performed, nor was any specific analysis performed to determine homogeneity of the results.

Aspirin is the first-line antiplatelet therapy for patients with ST-segment elevation myocardial infarction (MI). Aspirin or clopidogrel is recommended for patients with initial transient ischemic attack (TIA)/ischemic stroke, chronic stable angina, or peripheral arterial disease (because aspirin is less expensive, clopidogrel should be reserved only for aspirin-intolerant patients). Aspirin plus clopidogrel is recommended for patients with non–ST-segment elevation acute coronary syndrome.

For second-line therapy, the combination of aspirin and clopidogrel is recommended for recurrent acute coronary syndrome. The combination of aspirin and clopidogrel does not, however, lower the incidence of recurrent vascular events in patients with recurrent TIA/ischemic stroke, but does increase the risk of major and life-threatening bleeding. Therefore, the combination of aspirin and extended-release dipyridamole is recommended for patients with recurrent TIA/ischemic stroke in the absence of known coronary artery disease. Because dipyridamole may exacerbate myocardial ischemia, further studies are needed before firm recommendations can be made on the management of patients with recurrent TIA/ischemic stroke and known coronary artery disease.

Bottom Line: Aspirin is the recommended oral first-line antiplatelet therapy for patients with ST-segment elevation MI. Aspirin or clopidogrel is recommended for patients with initial TIA/ischemic stroke, chronic stable angina, or peripheral arterial disease, and aspirin plus clopidogrel should be used for patients with non–ST-segment elevation acute coronary syndrome. For second-line therapy, the combination of aspirin and clopidogrel is recommended for recurrent acute coronary syndrome. The combination of aspirin and extended-release dipyridamole is recommended for patients with recurrent TIA/ischemic stroke in the absence of known coronary artery disease. Further studies are needed before firm recommendations can be made on the management of patients with recurrent TIA/ischemic stroke and known coronary artery disease. (Level of Evidence: 1a–)