Tuesday, October 16, 2007

Reassessment of the cardiovascular risks of Rosiglitazone.

A recent meta-analysis of 42 clinical trials concluded that rosiglitazone was associated with an approximately 43% increased risk for myocardial infarction and an approximately 64% increased risk for cardiovascular death. The sensitivity of these conclusions to several methodological choices was not assessed. The meta-analysis was not based on a comprehensive search for all studies that might yield evidence about rosiglitazone’s cardiovascular effects. Studies were combined on the basis of a lack of statistical heterogeneity, despite substantial variability in study design and outcome assessment. The meta-analytic approach that was used required the exclusion of studies with zero events in the treatment and control groups. Alternative meta-analytic approaches that use continuity corrections show lower odds ratios that are not statistically significant. The authors of this commentary conclude that the risk for myocardial infarction and death from cardiovascular disease for diabetic patients taking rosiglitazone is uncertain - neither increased nor decreased risk is established.

The authors state that their analysis is restricted by the same limitations as those in the original analysis: short follow-up; low event rates; absence of patient-level data about time to event; variable and probably incomplete outcome ascertainment; and inability to reliably assess total mortality rate or composite outcomes, such as death or myocardial infarction. Neither analysis is a comprehensive systematic summary of all available evidence about the potential cardiovascular risks of rosiglitazone. Only prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone will resolve the controversy about its safety. They conclude that the available evidence does not justify the recommendations for action of the original study.

Ann Intern Med 7 Aug 2007 – Early online(to be published 16 October 2007)

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