Context: Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes. Objective: To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality. Data Sources: We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007. Study Selection: Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events. Data Extraction: Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n=14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years). Results: Rosiglitazone significantly increased the risk of myocardial infarction (n=94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P=.02) and heart failure (n=102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P<.001) without a significant increase in risk of cardiovascular mortality (n=59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P=.53). There was no evidence of substantial heterogeneity among the trials for these end points (I2=0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality). Conclusion Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.
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