Controversy emerged soon after the drug's introduction, when reports first suggested that the use of rosiglitazone and a related drug, pioglitazone, could precipitate congestive heart failure in susceptible individuals. The standards for approval of diabetes drugs during that era required only demonstration of the reduction of hemoglobin A 1c levels in trials of moderate duration (typically 24-52 weeks) in the absence of any apparent safety concerns. Rosiglitazone was initially approved in 1999 to treat hyperglycemia in patients with type 2 diabetes mellitus. 4 That study was limited by low event rates, which resulted in insufficient statistical power to confirm or refute evidence of an increased risk for ischemic myocardial events. 2, 3 No large, definitive CV outcomes trials have been conducted with rosiglitazone, although an open-label, noninferiority trial reported results in 2009 (RECORD ). 1 The debate over the CV safety of rosiglitazone therapy has continued during the past 3 years, recently receiving renewed attention after the release of a report from the US Senate Committee on Finance that provided additional details about internal analyses conducted by the maker of rosiglitazone, GlaxoSmithKline (GSK), and the US Food and Drug Administration (FDA). The current findings suggest an unfavorable benefit to risk ratio for rosiglitazone.Ĭontroversy regarding the cardiovascular safety of the diabetes drug rosiglitazone arose in 2007 after the publication of a meta-analysis that demonstrated a significantly elevated risk for myocardial infarction (MI) and a borderline significant increased risk for cardiovascular (CV) mortality. 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).Ĭonclusions 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. 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). Results Rosiglitazone therapy significantly increased the risk of MI (OR, 1.28 95% confidence interval, 1.02-1.63 P = .04) but not CV mortality (OR, 1.03 95% CI, 0.78-1.36 P = .86). Study Selection The study included all randomized controlled trials of rosiglitazone at least 24 weeks in duration that reported CV adverse events.ĭata 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. Objective To systematically review the effects of rosiglitazone therapy on MI and mortality (CV and all-cause).ĭata 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. Shared Decision Making and CommunicationĬontext 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.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.
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