Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial

AIMS To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT). METHODS Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI). RESULTS Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day. CONCLUSIONS In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI.