More Bad News for Rosiglitazone
For more than 10 years, thiazolidinediones (TZDs) have been prescribed for diabetes therapy in the U.S. on the sole basis of evidence that they improve glycemic control. An association of TZDs with heart failure is relatively well-established; however, recent data have implicated rosiglitazone in other adverse cardiovascular events as well.
Two new studies further address the risks of rosiglitazone. In an observational cohort study, 227,571 Medicare patients (median age, 74.4) began therapy with either rosiglitazone or pioglitazone between July 2006 and June 2009. During a median follow-up of 105 days, rosiglitazone recipients were significantly more likely than pioglitazone recipients to experience adverse events including stroke (hazard ratio, 1.27); heart failure (HR, 1.25); death from any cause (HR, 1.14); and a composite of acute myocardial infarction (AMI), stroke, heart failure, and death (HR, 1.18). The risk for AMI alone did not differ between the two groups. For the composite endpoint, the estimated overall number needed to harm was 60 patients treated for 1 year.
In an extension of a well-known 2007 meta-analysis of clinical trials of rosiglitazone (JW Cardiol May 21 2007), researchers examined 56 trials involving 35,531 patients randomized to receive rosiglitazone or a control therapy for more than 24 weeks. Treatments used in the control groups included placebo, usual care, and non-TZD antidiabetic therapies. Compared with controls, patients in the rosiglitazone groups had a significantly higher risk for MI (odds ratio, 1.28) but not for cardiovascular mortality. Separate analyses that either included or excluded studies with no adverse cardiovascular events yielded similar results.
Comment: These studies add to growing evidence that, despite lowering glucose levels, rosiglitazone causes important adverse cardiovascular events. The different rosiglitazone-associated adverse outcomes in the studies may be explained by differences in study designs, patient populations, comparison groups, lengths of follow-up, and methods of outcomes ascertainment. Although observational studies are prone to confounding, and meta-analyses have their own limitations, these findings will increase pressure on the FDA to reconsider whether rosiglitazone should remain on the market, bearing in mind the availability of pioglitazone, which appears to be a safer alternative.
— Frederick A. Masoudi, MD, MSPH
Published in Journal Watch Cardiology June 30, 2010
CITATION(S):
Graham DJ et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA 2010 Jun 28; [e-pub ahead of print]. (http://dx.doi.org/10.1001/jama.2010.920)
Juurlink DN. Rosiglitazone and the case for safety over certainty.JAMA 2010 Jun 28; [e-pub ahead of print]. (http://dx.doi.org/10.1001/jama.2010.954)
Nissen SE and Wolski K. Rosiglitazone revisited: An updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 2010 Jun 28; [e-pub ahead of print]. (http://dx.doi.org/10.1001/archinternmed.2010.207)
