Thiazolidinedione use is not associated with worse cardiovascular outcomes: A study in 28,332 high risk patients with diabetes in routine clinical practice: Brief title: Thiazolidinedione use and mortality

Objective: Assess the cardiovascular safety of Thiazolidinediones (TZD) in routine clinical practice. Background: TZD are insulin-sensitizing antidiabetic drugs commonly used in type 2 diabetes, but their cardiovascular safety has been questioned. We examined the association between TZD use and major cardiovascular outcomes. Methods: We examined 2-year mortality, non-fatal myocardial infarction (MI), and congestive heart failure (CHF) rates among outpatients with high cardiovascular risk and diabetes according to TZD use in the REACH Registry. Multivariable adjustment and propensity scores were used in the analyses. Results: A total of 4997 out of 28,332 patients took TZDs at baseline. During follow-up, 1532 patients died. The mortality rates (95% confidence interval [CI]) were 6.5% (5.5-7.6) with TZD and 7.2% (6.33-8.06) without; adjusted hazard ratio (HR) was 1.06 (0.89-1.26, P = 0.54). The lack of association with mortality was consistent across subgroups regardless of history of atherothrombosis or CHF. Rates of non-fatal MI (HR 1.10, 95% CI 0.83-1.45, P = 0.50) and non-fatal CHF (HR 0.90, CI 0.75-1.09, P = 0.27) were similar in users and non-users. TZD use was associated with an increased risk of CHF in patients aged > 80 years (HR 1.59, CI 1.06-2.40, P = 0.03). Conclusions: Use of TZD was not associated with increased incidence of major cardiovascular events in patients with diabetes from this large registry. Older patients experienced an increased risk of CHF over the study interval. Limitations of this study include its observational design, and thus unmeasured confounders cannot be excluded.