Background Rosiglitazone is widely used to treat patients withtype 2 diabetes mellitus, but its effect on cardiovascular morbidityand mortality has not been determined.
Methods We conducted searches of the published literature, theWeb site of the Food and Drug Administration, and a clinical-trialsregistry maintained by the drug manufacturer (GlaxoSmithKline).Criteria for inclusion in our meta-analysis included a studyduration of more than 24 weeks, the use of a randomized controlgroup not receiving rosiglitazone, and the availability of outcomedata for myocardial infarction and death from cardiovascularcauses. Of 116 potentially relevant studies, 42 trials met theinclusion criteria. We tabulated all occurrences of myocardialinfarction 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 approximately56 years, and the mean baseline glycated hemoglobin level wasapproximately 8.2%. In the rosiglitazone group, as comparedwith the control group, the odds ratio for myocardial infarctionwas 1.43 (95% confidence interval [CI], 1.03 to 1.98; P=0.03),and the odds ratio for death from cardiovascular causes was1.64 (95% CI, 0.98 to 2.74; P=0.06).
Conclusions Rosiglitazone was associated with a significantincrease in the risk of myocardial infarction and with an increasein the risk of death from cardiovascular causes that had borderlinesignificance. Our study was limited by a lack of access to originalsource data, which would have enabled time-to-event analysis.Despite these limitations, patients and providers should considerthe potential for serious adverse cardiovascular effects oftreatment with rosiglitazone for type 2 diabetes.
Source Information
From the Cleveland Clinic, Cleveland. This article (10.1056/NEJMoa072761) was published at www.nejm.org on May 21, 2007.
Address reprint requests to Dr. Nissen at the Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens{at}ccf.org.
Rosiglitazone and Cardiovascular Risk
Bracken M. B., Mannucci E., Monami M., Marchionni N., Diamond G. A., Kaul S., Brett A. S., Nissen S. E., Wolski K., Psaty B. M., Furberg C. D.
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N Engl J Med 2007;
357:937-940, Aug 30, 2007.
Correspondence
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A correction has been published: N Engl J Med 2007;357(1):100.
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