Recent studies have shown that glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin appear to be more beneficial in patients who are at higher risk for acute myocardial infarctions (MIs). Clopidogrel and aspirin act by directly reducing the degree of platelet activation. Using data from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial, Cannon and associates evaluated the hypothesis that patients with greater risk for developing acute MI would have a greater relative benefit from clopidogrel than from aspirin.

In the CAPRIE trial, the incidence of acute MI was determined during a follow-up of at least three years among three groups of patients with different risk factors for cardiovascular events, including the following: (1) recent ischemic stroke with persistent neurologic deficit and no evidence of cerebral hemorrhage; (2) acute MI within the previous 35 days; and (3) documented peripheral arterial disease. A comparison of baseline characteristics showed that patients who developed acute MI were slightly older and more frequently men, and had a higher rate of previous cardiac surgery and congestive heart failure. The comorbidity of diabetes, angina pectoris, prior ischemic stroke, peripheral artery disease, and elevated baseline creatinine levels also were predictive of an increased risk of acute MI. Treatment with clopidogrel was significantly associated with a decrease in the development of acute MI.

The risk of acute MI was less in all risk categories and combinations in patients who were treated with clopidogrel compared with patients who received aspirin. The difference was greatest among patients with at least five risk factors, among whom treatment with clopidogrel yielded a 5.1 percent absolute reduction (30 percent relative risk reduction) in the risk of acute MI over three years. Among participants with the lowest risk, clopidogrel provided a 1.2 percent absolute risk reduction (30 percent relative risk reduction). The risk reduction produced by treatment with clopidogrel was greater than that of aspirin across all risk groups.

Although previous studies have demonstrated that the greatest benefit of aggressive antithrombotic treatment occurs in high-risk patients, the authors conclude that their study demonstrates a similar relative risk reduction benefit of treatment with clopidogrel in patients with all ranges of risk factors. In the complete CAPRIE trial, clopidogrel produced an additional 8.7 percent reduction in cardiovascular death, acute MI, or ischemic stroke compared with aspirin.