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Is Clopidogrel Plus Aspirin Better than Aspirin Alone for Clinically Stable Patients?

Data from the CHARISMA trial suggest that the answer is no.

A role for short-term dual-antiplatelet therapy with aspirin and clopidogrel has been established for patients with unstable angina and acute myocardial infarction, and for patients undergoing angioplasty and stenting. In this industry-sponsored study (known as CHARISMA), researchers determined whether dual therapy is beneficial for a broader range of patients.

A total of 15,603 patients with either documented cardiovascular disease (coronary, cerebrovascular, or peripheral arterial disease) or multiple cardiovascular risk factors were randomized to receive aspirin plus either daily clopidogrel (75 mg) or placebo. Patients with established indications for clopidogrel (e.g., recent coronary syndrome) were excluded. During a median follow-up of 28 months, no significant difference was noted in the rate of the primary outcome (MI, stroke, or cardiovascular death) between the dual-therapy and aspirin-alone groups (6.8% vs. 7.3%, P=0.22). Patients who received dual therapy were slightly more likely than those who received aspirin alone to have severe bleeding (1.7% vs. 1.3%, P=0.09) or moderate bleeding (2.1% vs. 1.3%, P<0.001). In the subgroup of patients who qualified for the study because of multiple risk factors, the primary endpoint, as well as bleeding complications, occurred more often with dual therapy than with aspirin alone. In the subgroup of patients who were enrolled by virtue of clinically evident cardiovascular disease, dual therapy was associated with a small reduction in the primary endpoint (6.9% vs. 7.9%, P=0.046) and a small increase in moderate bleeding (2.1% vs. 1.3%, P<0.001) compared with aspirin alone.

Comment: In this trial, the combination of clopidogrel plus aspirin was not more effective than aspirin alone among patients with multiple risk factors or patients with established but stable cardiovascular disease. Although a hint of benefit was seen in the subgroup with established cardiovascular disease, the authors conclude that their findings do not support dual-antiplatelet therapy "across the broad population tested." An editorialist concurs, stating that "extracting favorable P values from subgroups should be resisted."

— Allan S. Brett, MD

Published in Journal Watch General Medicine March 21, 2006

Citation(s):

Bhatt DL et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006 Apr 20; 354. (http://dx.doi.org/10.1056/NEJMoa060989)

Pfeffer MA and Jarcho JA. The charisma of subgroups and the subgroups of CHARISMA. N Engl J Med 2006 Apr 20; 354. (http://dx.doi.org/10.1056/NEJMe068061)

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