Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial

Abstract

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.

Keywords: cardiovascular disease; older adults; rosiglitazone; type 2 diabetes.

Figure 1

Effect of rosiglitazone dosage on time to (A) primary composite cardiovascular (CV) event and (B) CV death. *Baseline and **time-dependent covariates include: age, race, smoking status, diabetes duration, previous CV event, glycated haemoglobin, baseline and on-study body mass index, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, severe hypoglycaemic episodes and baseline and on-study use of insulin, other oral agents, statins and aspirin.

Figure 2

Effect of rosiglitazone dosage on time to (A) myocardial infarction and (B) coronary revascularization. *Baseline and **time-dependent covariates include: age, race, smoking status, diabetes duration, previous cardiovascular event, glycated haemoglobin, baseline and on-study BMI, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, severe hypoglycaemic episodes, and baseline and on-study use of insulin, other oral agents, statins and aspirin.

Figure 3

Rosiglitazone use in cases and controls according to myocardial infarction, coronary revascularization, cardiovascular (CV) death or primary CV outcome. (A) Percentage of cases and controls who had at least one prescription for rosiglitazone over the course of the study. (B) Average daily rosiglitazone dose in cases and controls.