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Previous Volume 355:1551-1562 October 12, 2006 Number 15 Next

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ABSTRACT

Background Previous studies have suggested that blockade of the renin–angiotensin system may prevent diabetes in people with cardiovascular disease or hypertension.

Methods In a double-blind, randomized clinical trial with a 2-by-2 factorial design, we randomly assigned 5269 participants without cardiovascular disease but with impaired fasting glucose levels (after an 8-hour fast) or impaired glucose tolerance to receive ramipril (up to 15 mg per day) or placebo (and rosiglitazone or placebo) and followed them for a median of 3 years. We studied the effects of ramipril on the development of diabetes or death, whichever came first (the primary outcome), and on secondary outcomes, including regression to normoglycemia.

Results The incidence of the primary outcome did not differ significantly between the ramipril group (18.1%) and the placebo group (19.5%; hazard ratio for the ramipril group, 0.91; 95% confidence interval [CI], 0.81 to 1.03; P=0.15). Participants receiving ramipril were more likely to have regression to normoglycemia than those receiving placebo (hazard ratio, 1.16; 95% CI, 1.07 to 1.27; P=0.001). At the end of the study, the median fasting plasma glucose level was not significantly lower in the ramipril group (102.7 mg per deciliter [5.70 mmol per liter]) than in the placebo group (103.4 mg per deciliter [5.74 mmol per liter], P=0.07), though plasma glucose levels 2 hours after an oral glucose load were significantly lower in the ramipril group (135.1 mg per deciliter [7.50 mmol per liter] vs. 140.5 mg per deciliter [7.80 mmol per liter], P=0.01).

Conclusions Among persons with impaired fasting glucose levels or impaired glucose tolerance, the use of ramipril for 3 years does not significantly reduce the incidence of diabetes or death but does significantly increase regression to normoglycemia. (ClinicalTrials.gov number, NCT00095654 [ClinicalTrials.gov] .)

Source Information

The members of the Writing Committee (Jackie Bosch, M.Sc., Salim Yusuf, D.Phil., Hertzel C. Gerstein, M.D., Janice Pogue, M.Sc., Patrick Sheridan, M.Sc., McMaster University, Hamilton; Gilles Dagenais, M.D., Laval University Heart and Lung Institute, Quebec; Jean Louis Chiasson, M.D., Research Centre–Centre Hospitalier de l'Université de Montreal–Hôtel-Dieu, Montreal — all in Canada; Rafael Diaz, M.D., Instituto Cardiovascular de Rosario, Rosario, Argentina; Alvaro Avezum, Ph.D., Dante Pazzanese Institute of Cardiology, São Paulo, Brazil; Fernando Lanas, M.D., Universidad de la Frontera, Temuco, Chile; Jeffrey Probstfield, M.D., Fred Hutchinson Cancer Research Center, Seattle; George Fodor, Ph.D., University of Ottawa Heart Institute, Ottawa; and Rury R. Holman, F.R.C.P., Oxford Centre for Diabetes, Endocrinology, and Metabolism, Oxford, United Kingdom) of the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial assume responsibility for the overall content and integrity of the article.

This article was published at www.nejm.org on September 15, 2006.

Address reprint requests to the DREAM Project Office, Population Health Research Institute, 2nd Fl., McMaster Clinic, 237 Barton St. E, Hamilton, ON L8L 2X2, Canada, or to dream{at}cardio.on.ca.

Full Text of this Article

Related Letters:

Effect of Ramipril on the Incidence of Diabetes
Bangalore S., Messerli F. H., Potter B. J., LeLorier J., Epstein B. J., Cooper-DeHoff R. M., Bosch J., Yusuf S., Gerstein H.
Extract | Full Text | PDF  
N Engl J Med 2007; 356:522-524, Feb 1, 2007. Correspondence

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