Cardiac safety profile of rosiglitazone. A comprehensive meta-analysis of randomized clinical trials

Abstract BACKGROUND: Some meta-analyses of randomized clinical trials suggested that rosiglitazone could be associated with increased risk for myocardial infarction (MI). Available meta-analyses, based on studies sponsored by GlaxoSmithKline (GSK), failed to include all trials performed with rosiglitazone. Aim of this analysis is the assessment of the cardiovascular risk with rosiglitazone, using a comprehensive data set. METHODS: Results of 164 trials with duration >4 weeks were retrieved from http://ctr.gsk.co.uk/welcome.asp and from Medline, while unpublished studies were identified from www.clinicaltrials.gov. A total of 164 trials (42,922 and 45,483 patient years for rosiglitazone and comparators, respectively) were included in the analysis. RESULTS: The OR for all-cause and cardiovascular mortality with rosiglitazone was 0.93[0.76;1.14] and 0.94[0.68;1.29], respectively; rosiglitazone-associated risk for nonfatal MI and heart failure was 1.14[0.90;1.45] and 1.69[1.21;2.36], respectively. The risk of heart failure was higher (2.20[1.28;3.78]) when rosiglitazone was administered as add-on therapy to insulin. CONCLUSIONS: Figures for rosiglitazone-associated risk for myocardial infarction could be lower than those previously reported on the basis of a smaller number of clinical trials. No increase of all-cause or cardiovascular mortality were observed with rosiglitazone. Conversely, treatment with rosiglitazone is associated with a relevant increase in the risk of heart failure, particularly in insulin-treated patients.