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.