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Clopidogrel has been evaluated across the spectrum of secondary and primary prevention. Initially, the CAPRIE trial randomized patients with recent myocardial infarction, ischemic stroke or symptomatic peripheral arterial disease to either clopidogrel or aspirin and followed them for up to three years. That study found clopidogrel to be superior to aspirin, with subsequent post hoc analyses finding the greatest benefit in higher risk subgroups. Favorable data from multiple clinical trials of aspirin plus clopidogrel in percutaneous coronary intervention and acute coronary syndromes led to the CHARISMA study. This trial randomized patients to clopidogrel plus aspirin versus placebo plus aspirin for a median of 28 months. Patients with stable coronary artery disease, cerebrovascular disease, or peripheral arterial disease (meant to represent secondary prevention) or with multiple risk factors (meant to represent primary prevention) were enrolled. The trial did not find a significant reduction in cardiovascular death, myocardial infarction, or stroke with dual antiplatelet therapy in the overall population, though the subgroup of patients with documented cardiovascular disease did appear to have some benefit. Further analysis of the CHARISMA data set and future trials should further refine which patients are most likely to benefit from intensification of antithrombotic therapy beyond aspirin alone.

Clinical evaluation of clopidogrel across the whole spectrum of indications: primary and secondary prevention of coronary artery disease