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Background In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.
Methods After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.
Results Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001).
Conclusions Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101
[ClinicalTrials.gov]
.)
Source Information
The members of the writing committee (Salim Yusuf, D.Phil., Koon K. Teo, Ph.D., Janice Pogue, M.Sc., Leanne Dyal, M.Sc., and Ingrid Copland, Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; Helmut Schumacher, Ph.D., Boehringer Ingelheim, Ingelheim, Germany; Gilles Dagenais, M.D., Laval University Heart and Lung Institute, Laval Hospital, Quebec, QC, Canada; Peter Sleight, D.M., Oxford University, Oxford, United Kingdom; and Craig Anderson, Ph.D., George Institute for International Health, University of Sydney, Sydney) assume responsibility for the overall content and integrity of the article.
This article (10.1056/NEJMoa0801317) was published at www.nejm.org on March 31, 2008.
Address reprint requests to Dr. Yusuf at the Population Health Research Institute, Hamilton Health Sciences and McMaster University, 237 Barton St. East, Hamilton, ON L8L 2X2, Canada, or at yusufs{at}mcmaster.ca.
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