Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.

Abstract

BACKGROUND In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events. METHODS AND RESULTS The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047). CONCLUSIONS In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.