Effects of ramipril and rosiglitazone on cardiovascular and renal outcomes in people with impaired glucose tolerance or impaired fasting glucose: a randomized, controlled trial. Results of the diabetes reduction assessment with ramipril and rosiglitazone medication (DREAM) study

Abstract

Objective: Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD) and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. Research Design and Methods: 5269 people aged = 30 years, with IGT and/or IFG without known CVD or renal insufficiency were randomized to ramipril 15 mg/day vs. placebo, and rosiglitazone 8 mg/day vs. placebo. A composite cardio-renal outcome and its CVD and renal components were assessed during the 3-year follow-up. Results: Compared to placebo, neither ramipril [15.7%, (412/2623) vs. 16.0%, (424/2646)] [Hazard ratio (HR) 0.98 (95% CI, 0.84 - 1.13) P = 0.75], nor rosiglitazone [15.0% (394/2635) vs. 16.8% (442/2634)] [HR 0.87 (CI, 0.75 - 1.01) P = 0.07] reduced the risk of the cardio-renal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure [0.53 vs. 0.08%, HR 7.04 (CI, 1.60 - 31.0) P = 0.01] but reduced the risk of the renal component [HR 0.80 (CI, 0.68 - 0.93) P = 0.005]; prevention of diabetes was independently associated with prevention of the renal component (P < 0.001). Conclusions: Ramipril did not alter the cardio-renal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardio-renal outcome and increased the risk of heart failure.