The new england JOURNAL of MEDICINE ESTABLISHED IN 181 JUNE14,2007 V0L.356N0.2 Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes Steven E.Nissen,M.D.,and Kathy Wolski,M.P.H. ABSTRACT BACKGROUND iglit mellitus,but its reprint Dr. the D METHODS We conducted searches of the published literature,the Web site of the Food and org Drug Administration,and a ceri for inclusion in our meta-analysis included a (G. 2007 rdialp tion and death fro s.0f116p 47 NEng]Med2007,35624577 trials met the inclusion criteria.We tabulated all occurrences of myocardial infare- tion and death from cardiovascular causes. RESULTS with the control group,the odds ratio for myocardial infarction was 1.43(95% confidence interval [CI],1.03 to 1.98;P=0.03),and the odds ratio for death from cardiovascular causes was 1.64(95%CL 0.98 to 2.74:P=0.06). ignificance.Our study was limited by a lack of access to original source data.which would have enabled time-to-vent.Despite these limita tions,patients and providers should consider the potential for serious adverse car- diovascular effects of treatment with rosiglitazone for type 2 diabetes. N ENGL J MED 356;24 WWW.NEJM.ORG JUNE 14,200 2457 The New England Joumal of Medicine n engl j med 356;24 www.nejm.org june 14, 2007 2457 The new england journal of medicine established in 1812 june 14, 2007 vol. 356 no. 24 Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes Steven E. Nissen, M.D., and Kathy Wolski, M.P.H. A bs tr ac t From the Cleveland Clinic, Cleveland. Ad￾dress reprint requests to Dr. Nissen at the Department of Cardiovascular Medi￾cine, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens@ccf. org. This article (10.1056/NEJMoa072761) was published at www.nejm.org on May 21, 2007. N Engl J Med 2007;356:2457-71. Copyright © 2007 Massachusetts Medical Society. Background Rosiglitazone is widely used to treat patients with type 2 diabetes mellitus, but its effect on cardiovascular morbidity and mortality has not been determined. Methods We conducted searches of the published literature, the Web site of the Food and Drug Administration, and a clinical-trials registry maintained by the drug manu￾facturer (GlaxoSmithKline). Criteria for inclusion in our meta-analysis included a study duration of more than 24 weeks, the use of a randomized control group not receiving rosiglitazone, and the availability of outcome data for myocardial infarc￾tion and death from cardiovascular causes. Of 116 potentially relevant studies, 42 trials met the inclusion criteria. We tabulated all occurrences of myocardial infarc￾tion and death from cardiovascular causes. Results Data were combined by means of a fixed-effects model. In the 42 trials, the mean age of the subjects was approximately 56 years, and the mean baseline glycated hemoglobin level was approximately 8.2%. In the rosiglitazone group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03), and the odds ratio for death from cardiovascular causes was 1.64 (95% CI, 0.98 to 2.74; P=0.06). Conclusions Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limita￾tions, patients and providers should consider the potential for serious adverse car￾diovascular effects of treatment with rosiglitazone for type 2 diabetes. The New England Journal of Medicine Downloaded from nejm.org on February 5, 2016. For personal use only. No other uses without permission. Copyright © 2007 Massachusetts Medical Society. All rights reserved