Thiazolidinediones and Heart Failure

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Abstract
Thiazolidinediones (TZDs) are known to increase the risk of heart failure in patients with type 2 diabetes. We aimed to evaluate the magnitude of the risk of heart failure with TZDs and classify this adverse effect under the novel dose-time-susceptibility system. Evidence from randomized trials, controlled observational studies, anecdotal case reports, case series, and spontaneous reports in the Canadian Drug Reaction Monitoring Program (CADRMP) was analyzed in a teleo-analysis. A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years. Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs.