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Salim Yusuf, DPhil,FRCPC; Hertzel Gerstein, FRCP; Byron Hoogwerf, MD; Janice Pogue, MSc; Jackie Bosch, MSc; Bruce H. R. Wolffenbuttel, MD; Bernard Zinman, FRCP; for the HOPE Study Investigators

JAMA. 2001;286:1882-1885.

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 confirmation.

Author Affiliations: McMaster University, Hamilton, Canada (Drs Yusuf and Gerstein and Mss Pogue and Bosch); Cleveland Clinic Foundation, Cleveland, Ohio (Dr Hoogwerf); Clinic of Maastricht, Maastricht, the Netherlands (Dr Wolffenbuttel); Mt Sinai and Toronto Hospitals, Toronto, Canada (Dr Zinman). A complete list of the HOPE investigators has been previously published.¹¹

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