Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients

Background Angiotensin-converting-enzyme inhibitors improve the outcome amo ng patients with left ventricular dysfunction, whether or not they have hea rt failure. We assessed the role of an angiotensin-converting-enzyme inhibi tor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. Methods A total of 9297 high-risk patients (55 years of age or older) who h ad evidence of vascular disease or diabetes plus one other cardiovascular r isk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day oral ly) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular c auses. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. Results A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 pe rcent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as comp ared with 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. 4.9 percent; 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; rel ative risk, 0.85; P=0.002), cardiac arrest (0.8 percent vs. 1.3 percent; re lative risk, 0.63; P=0.03), heart failure (9.0 percent vs. 11.5 percent; re lative risk, 0.77; P<0.001), and complications related to diabetes (6.4 per cent vs. 7.6 percent; relative risk, 0.84; P=0.03). Conclusions Ramipril significantly reduces the rates of death, myocardial i nfarction, and stroke in a broad range of high-risk patients who are not kn own to have a low ejection fraction or heart failure. (N Engl J Med 2000;34 2:145-53.) (C) 2000, Massachusetts Medical Society.