Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left
ventricular dysfunction, whether or not they have heart failure. We assessed the role
of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high
risk for cardiovascular events but who did not have left ventricular dysfunction or
heart failure.
A total of 9297 high-risk patients (55 years of age or older) who had evidence of
vascular disease or diabetes plus one other cardiovascular risk 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 orally) or matching placebo for a mean of
five years. The primary outcome was a composite of myocardial infarction, stroke,
or death from cardiovascular causes. 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.
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 percent 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 compared 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 (16.3 percent vs. 18.8 percent; relative risk, 0.85;
P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02),
[corrected] heart failure (9.1 percent vs. 11.6 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).
Ramipril significantly reduces the rates of death, myocardial infarction, and stroke
in a broad range of high-risk patients who are not known to have a low ejection fraction
or heart failure.