Ramipril and the development of diabetes

Ramipril and the development of diabetes. Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH, Zinman B; HOPE Study Investigators. Canadian Cardiovascular Collaboration Project Office, Hamilton General Hospital, 237 Barton St East, Hamilton, Ontario, Canada L8L 2X2. yusufs@mcmaster.ca CONTEXT: Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied. OBJECTIVE: To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons. DESIGN, SETTING, AND PARTICIPANTS: The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999. INTERVENTION: Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883). MAIN OUTCOME MEASURE: Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups. RESULTS: One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined. CONCLUSIONS: Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmatio