CHARISMA Trial data indicate that clopidogrel plus aspirin has no added benefit beyond aspirin alone to prevent myocardial infarction and ischemic stroke, although the benefit-to-risk analysis differed for identifiable subgroups, according to a presentation at the annual meeting of the American College of Cardiology.

The international trial enrolled 15,603 patients aged 45 years or older who had clinically evident cardiovascular disease or had multiple risk factors to one or two study arms: clopidogrel 75 mg daily plus aspirin 75-162 mg daily or placebo plus aspirin. Median follow-up was 28 months.

The primary endpoint was the composite of myocardial infarction, stroke, or cardiovascular-related death. Overall, the addition of clopidogrel to aspirin therapy produced a nonsignificant decrease in risk of the primary endpoint (6.8 percent in clopidogrel plus aspirin group and 7.3 in the aspirin-only group). However, the rate of moderate-to-severe bleeding was increased in patients taking clopidogrel compared to the rate in those taking placebo.

However, investigators did not some interesting trends for the patient subgroups of adults with clinically evident disease versus those with multiple risk factors. A possible benefit of clopidogrel was seen in patients with clinically evident atherothrombotic disease (6.9 percent clopidogrel plus aspirin group and 7.9 percent in the aspirin-only group, a 0.88 relative risk).

An opposite effect of clopidogrel, a possible harm, was seen for patients who had multiple risk factors: The rate of the primary end point was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2) and the rate of death from cardiovascular causes was higher with clopidogrel (3.9 percent vs. 2.2 percent).