Background Angiotensin-converting–enzyme inhibitors improvethe outcome among patients with left ventricular dysfunction,whether or not they have heart failure. We assessed the roleof an angiotensin-converting–enzyme inhibitor, ramipril,in patients who were at high risk for cardiovascular eventsbut who did not have left ventricular dysfunction or heart failure.
Methods A total of 9297 high-risk patients (55 years of ageor older) who had evidence of vascular disease or diabetes plusone other cardiovascular risk factor and who were not knownto have a low ejection fraction or heart failure were randomlyassigned to receive ramipril (10 mg once per day orally) ormatching placebo for a mean of five years. The primary outcomewas a composite of myocardial infarction, stroke, or death fromcardiovascular causes.
The trial was a two-by-two factorial study evaluating both ramipriland vitamin E. The effects of vitamin E are reported in a companionpaper.
Results A total of 651 patients who were assigned to receiveramipril (14.0 percent) reached the primary end point, as comparedwith 826 patients who were assigned to receive placebo (17.8percent) (relative risk, 0.78; 95 percent confidence interval,0.70 to 0.86; P<0.001). Treatment with ramipril reduced therates of death from cardiovascular causes (6.1 percent, as comparedwith 8.1 percent in the placebo group; relative risk, 0.74;P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent;relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9percent; relative risk, 0.68; P<0.001), death from any cause(10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005),revascularization procedures (16.0 percent vs. 18.3 percent;relative risk, 0.85; P=0.002), cardiac arrest (0.8 percent vs.1.3 percent; relative risk, 0.63; P=0.03), heart failure (9.0percent vs. 11.5 percent; relative risk, 0.77; P<0.001),and complications related to diabetes (6.4 percent vs. 7.6 percent;relative risk, 0.84; P=0.03).
Conclusions Ramipril significantly reduces the rates of death,myocardial infarction, and stroke in a broad range of high-riskpatients who are not known to have a low ejection fraction orheart failure.
Source Information
The writing group (Salim Yusuf, D.Phil., Peter Sleight, D.M., Janice Pogue, M.Sc., Jackie Bosch, M.Sc., Richard Davies, Ph.D., and Gilles Dagenais, M.D.) assumes responsibility for the overall content and integrity of the manuscript.
Address reprint requests to Dr. Salim Yusuf at the Canadian Cardiovascular Collaboration Project Office, Hamilton General Hospital, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at hope{at}ccc.mcmaster.ca.
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A correction has been published: N Engl J Med 2000;342(10):748.
