Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study Koon-Hou Mak, MD, a Deepak L. Bhatt, MD, b Mingyuan Shao, MS, c Graeme J. Hankey, MD, d J. Donald Easton, MD, e Keith A.A. Fox, MB, ChB, f and Eric J. Topol, MD g Singapore, Singapore; Boston, MA; Cleveland, OH; Perth, Australia; Providence, RI; Edinburgh, UK; and La Jolla, CA Background Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy. Methods This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding. Results The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613 (10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients. Conclusion In this trial of individuals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians). (Am Heart J 2009;157:658-65.) Atherothrombosis, consisting of coronary artery, cere- brovascular, and peripheral vascular diseases, is a major cause of morbidity and mortality worldwide. Several medical advances have improved the outcomes of these patients. However, there are marked differences in the rate, natural history, and outcomes of cardiovascular disease among individuals from various ethnic groups. 1 Even in a small closely knitted society with freely accessible health care such as Singapore, the incidence, and short- and long-term case fatality of acute coronary events varied considerably among different ethnic groups. 2 Although variations in risk factors and cultural background 3 may account for these differences, others have attributed these variations to access to health care facilities, availability of resources, care-seeking behavior, religious beliefs, socioeconomic factors, and adherence to evidence-based therapies. Indeed, clinical management and adverse event rates vary among different geographical regions and ethnic groups. 4,5 However, most of this information was derived from international registries that did not provide specific guidance on how patients were to be treated. Importantly, physician and patient beliefs, practices, and preferences also might have contributed to these differences. The CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial randomly assigned 15,603 patients with established atherothrombotic disease or multiple cardiovascular risk factors to either clopidogrel plus aspirin or placebo plus aspirin. 6 After From the a Gleneagles Medical Centre, Singapore, Singapore, b VA Boston Healthcare System and Brigham and Women's Hospital, Boston, MA, c Cleveland Clinic, Cleveland, OH, d Department of Neurology, Royal Perth Hospital and School of Medicine and Pharmacology, University of Western Australia, Perth, Australia, e Department of Neurology, Rhode Island Hospital and Brown University, Providence, RI, f University and Royal Infirmary of Edinburgh, Edinburgh, UK, and g Scripps Translational Research Institute, La Jolla, CA. The CHARISMA trial is registered with ClinicalTrials.gov, NCT00050817. Submitted April 13, 2008; accepted August 20, 2008. Reprint requests: Koon-Hou Mak, MD, Gleneagles Medical Centre, 6 Napier Road #08- 13, Singapore 258499. E-mail: makheart@gmail.com 0002-8703/$ - see front matter © 2009, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2008.08.031