Effectiveness of clopidogrel versus aspirin in preventing acute myocardial infarction in patients with symptomatic atherothrombosis (CAPRIE trial).

Article Outline• ReferencesBased on recent results with glycoprotein IIb/IIIa inhibitors and low molecular weight heparin having a greater relative benefit in higher risk groups,[1 and 2] we hypothesized that acute myocardial infarction (AMI) could be predicted with baseline characteristics and that patients at a higher risk of developing AMI would have a greater relative benefit from clopidogrel than from aspirin in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial.The design and results of the CAPRIE trial have been previously reported.[3] In brief, 3 groups of patients were eligible: patients with an ischemic stroke at least 1 week but less than 6 months before randomization, with a persistent neurologic deficit and no evidence of cerebral hemorrhage; patients with AMI within the prior 35 days; and patients with documented peripheral arterial disease, defined as patients with intermittent claudication and an ankle/brachial systolic blood pressure index of ≤0.85 in either leg on 2 separate occasions, or prior leg amputation or angioplasty. Exclusion criteria included uncontrolled hypertension, severe renal or hepatic insufficiency, a history of a bleeding disorder, or abnormal white or red blood cell counts. Informed consent was obtained from all but 10 patients before randomization. Patients were treated and followed for ≤3 years, with an average follow-up of 1.9 years.Patients were divided into 2 groups: those who did versus those who did not develop AMI during follow-up. AMI was defined as the presence of ≥2 of the following 3 criteria: (1) characteristic ischemic pain lasting ≥20 minutes; (2) elevation of creatine kinase or creatine kinase-MB, lactate dehydrogenase, or aspartate aminotransferase ≥2 times the upper limit of normal with no other explanation; (3) development of new Q waves of at least 0.4 mV in 2 adjacent electrocardiographic leads or a new dominant R wave in lead V1 (with the R wave ≥1 mm greater than the S wave in V1). A central validation committee that was blinded to treatment assignment adjudicated all outcomes.Baseline clinical factors were compared between patients who developed a documented AMI during the subsequent follow-up (1 to 3 years) and those who did not. The factors that were found to be significantly different were entered into a multivariate analysis to identify independent predictors of AMI. The odds ratio and 95% confidence intervals were calculated from multivariate analysis. From this list, the significant factors were selected as a risk score and the number of risk factors was assigned to each individual patient in the trial. Then, the rate of AMI during follow-up was assessed according to the number of risk factors. This latter analysis was then stratified by study drug assignment.Of the total 19,185 patients, a new AMI developed in 617 patients. Kaplan-Meier event rates showed that in patients treated with aspirin, 5.04% developed AMI during follow-up (1 to 3 years) compared with 4.2% of patients treated with clopidogrel, a 19.2% relative risk reduction (p = 0.008) (Figure 1). The relative benefit was constant over time.