CHARISMA: Two Anti-platelet drugs beneficial in secondary prevention, harmful in primary prevention

The Clopidogrel for High Atherothrombotic Risk for Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial showed no significant benefit for clopidogrel plus aspirin on clinical outcomes in the median 28-months follow-up in the 15,603 patients with either documented cardiovascular disease or multiple risk factors for atherosclerosis. The patients were randomized clopidogrel 75 mg daily or placebo, all patients received low-dose aspirin. Dr. Deepak Bhatt, Cleveland Clinic Foundation, presented the CHARISMA data at the American College of Cardiology meeting, and it was published online simultaneously in the New England Journal of Medicine. Dr. Bhatt stated that the initial hypothesis that two agents would be useful in a broad population was not met. Although the trial was negative, it did provide some intriguing findings for a difference in primary and secondary prevention patients.

Cardiovascular mortality, myocardial infarction (MI) or stroke occurred in 7.3% of the placebo plus aspirin group, compared to 6.8% in the clopidogrel plus aspirin group (p=0.22). However, a significant reduction with clopidogrel was found when hospitalization for an ischemic event was added to the endpoint, from 17.9% in the placebo plus aspirin group to 16.7% in the clopidogrel plus aspirin group.

In the 12,153 patients with established cardiovascular disease, that is, secondary prevention, clopidogrel reduced the combined rate of cardiovascular mortality, MI, or stroke from 7.9% in the placebo plus aspirin to 6.9% in the clopidogrel plus aspirin group; a 12.5% relative risk reduction and 1% absolute risk reduction.

No significant increase in severe bleeding was seen in patients with established cardiovascular disease (p=0.09). However, in patients with multiple risk factors, that is, primary prevention patients, clopidogrel may increase the risk of bleeding and mortality.