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±9years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4mg and 8mg 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 [4mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8mg: 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 8mg/day rosiglitazone); however, the effect on MI was less evident for 8mg/day and not significant for 4mg/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.