Background In patients who have vascular disease or high-riskdiabetes without heart failure, angiotensin-converting–enzyme(ACE) inhibitors reduce mortality and morbidity from cardiovascularcauses, 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 inpatients with vascular disease or high-risk diabetes.
Methods After a 3-week, single-blind run-in period, patientsunderwent double-blind randomization, with 8576 assigned toreceive 10 mg of ramipril per day, 8542 assigned to receive80 mg of telmisartan per day, and 8502 assigned to receive bothdrugs (combination therapy). The primary composite outcome wasdeath from cardiovascular causes, myocardial infarction, stroke,or hospitalization for heart failure.
Results Mean blood pressure was lower in both the telmisartangroup (a 0.9/0.6 mm Hg greater reduction) and the combination-therapygroup (a 2.4/1.4 mm Hg greater reduction) than in the ramiprilgroup. At a median follow-up of 56 months, the primary outcomehad 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 hadlower 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 samein the two groups (0.2%). In the combination-therapy group,the primary outcome occurred in 1386 patients (16.3%; relativerisk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramiprilgroup, 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), andrenal dysfunction (13.5% vs. 10.2%, P<0.001).
Conclusions Telmisartan was equivalent to ramipril in patientswith vascular disease or high-risk diabetes and was associatedwith less angioedema. The combination of the two drugs was associatedwith more adverse events without an increase in benefit. (ClinicalTrials.govnumber, 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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