Indications for Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Evidence-Based Recommendations for Use

OBJECTIVE: To review the literature assessing dual antiplatelet therapy with aspirin and clopidogrel and subsequently provide evidence-based recommendations for appropriate indications and length of therapy. DATA SOURCES: An English-language MEDLINE search (1950-December 2007) was conducted using the search terms antiplatelet, aspirin, thienopyridine, and clopidogrel to identify articles assessing dual antiplatelet therapy. Evaluation of references from identified trials for possible inclusion was also conducted. STUDY SELECTION AND DATA EXTRACTION: All studies that assessed treatment with the combination of aspirin and clopidogrel for any indication were included. DATA SYNTHESIS: Aspirin and clopidogrel have complementary mechanisms of action to inhibit platelet function. Indications that have been studied include coronary artery disease (CAD), atherosclerotic ischemic stroke, and atrial fibrillation. This combination has been beneficial in patients with acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), and in PCI patients without an acute event. There is a small but significant risk for increased bleeding with dual antiplatelet therapy for these indications. When used in patients with a history of atherosclerotic ischemic stroke or for prevention of cardioembolic stroke in patients with atrial fibrillation, this combination has been shown to increase bleeding, providing no clinical benefit, and to increase outcomes including stroke, myocardial infarction, and death, respectively. CONCLUSIONS: There is evidence to support use of aspirin in combination with clopidogrel for patients presenting with all ACS types, as well as for patients presenting with PCI for any indication. The treatment duration varies, but patients who have received stenting should receive at least 1 year of combination therapy. There is no evidence to support this combination for primary prevention of CAD or atherosclerotic ischemic events, secondary prevention of stable CAD, or prevention of cardioembolic stroke in patients with atrial fibrillation. The possible benefits of dual antiplatelet therapy also must be weighed against the risk of bleeding.