Rosiglitazone Revisited

CONTEXT: Controversy regarding the effects of rosiglitazone therapy on myocardial infarction (MI) and cardiovascular (CV) mortality persists 3 years after a meta-analysis initially raised concerns about the use of this drug. OBJECTIVE: To systematically review the effects of rosiglitazone therapy on MI and mortality (CV and all-cause). DATA SOURCES: We searched MEDLINE, the Web site of the Food and Drug Administration, and the GlaxoSmithKline clinical trials registry for trials published through February 2010. STUDY SELECTION: The study included all randomized controlled trials of rosiglitazone at least 24 weeks in duration that reported CV adverse events. DATA EXTRACTION: Odds ratios (ORs) for MI and mortality were estimated using a fixed-effects meta-analysis of 56 trials, which included 35 531 patients: 19 509 who received rosiglitazone and 16 022 who received control therapy. RESULTS: Rosiglitazone therapy significantly increased the risk of MI (OR, 1.28; 95% confidence interval CI, 1.02-1.63; P = .04) but not CV mortality (OR, 1.03; 95% CI, 0.78-1.36; P = .86). Exclusion of the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes) trial yielded similar results but with more elevated estimates of the OR for MI (OR, 1.39; 95% CI, 1.02-1.89; P = .04) and CV mortality (OR, 1.46; 95% CI, 0.92-2.33; P = .11). An alternative analysis pooling trials according to allocation ratios allowed inclusion of studies with no events, yielding similar results for MI (OR, 1.28; 95% CI, 1.01-1.62; P = .04) and CV mortality (OR 0.99; 95% CI, 0.75-1.32; P = .96). CONCLUSIONS: Eleven years after the introduction of rosiglitazone, the totality of randomized clinical trials continue to demonstrate increased risk for MI although not for CV or all-cause mortality. The current findings suggest an unfavorable benefit to risk ratio for rosiglitazone.