Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.

BACKGROUND: Clopidogrel is a more potent antiplatelet agent than aspirin, resulting in greater clinical efficacy in patients with atherothrombotic disease. Furthermore, the combination of clopidogrel plus aspirin has been demonstrated to be superior to aspirin alone in the treatment of patients with acute coronary syndromes and after coronary stenting. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention and secondary prevention is unknown.

METHODS AND RESULTS: The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study was designed to evaluate the efficacy and safety of clopidogrel plus aspirin versus placebo plus aspirin in patients with established coronary, cerebral, or peripheral arterial disease or in patients with multiple risk factors for atherothrombosis who have not yet sustained an ischemic event. This randomized, international, multicenter, double-blinded, placebo-controlled study has finished enrolling patients worldwide. A total of 15,603 patients will be followed long term. The primary end point will be the composite of vascular death, myocardial infarction, or stroke. Rates of severe bleeding will also be compared between the two arms of the study.

CONCLUSIONS: This large-scale trial of patients at high risk for atherothrombotic events will allow determination of the value of a strategy of adding clopidogrel to the current standard of care, including low-dose aspirin, for a wide spectrum of patients with atherothrombosis.