Long-term anti-ischemic effects of angiotensin-converting enzyme inhibition in patients after myocardial infarction

Objectives. This study was conducted to test the hypothesis that angiotensin-converting enzyme (ACE) inhibition reduces myocardial ischemia and related events after myocardial infarction (MI).

Background. The oxygen demand/supply ratio of the myocardium is influenced by angiotensin II as a result of its arterial vasoconstrictive and inotropic effects and through its interaction with the sympathetic nervous system.

Methods. We studied 244 patients who had been included in a double-blind, randomized, placebo-controlled, post-MI, ACE inhibition intervention study (Captopril and Thrombolysis Study [CATS]). All patients underwent exercise testing before and 3 and 12 months after hospital discharge. After 1-year double-blind treatment, all patients continued receiving single-blind placebo for 1 month.

Results. Total exercise time increased in both groups after 3 months (placebo: +86 +/- 13 s; captopril: +69 +/- 12 s, p = 0.8 between groups) and increased further after 1 year (placebo: +13 +/- 11 s; captopril: +33 +/- 13 s, p = 0.7 between groups). There were also no differences in mean ST segment depression. During the 12 months, significantly fewer ischemia related events occurred in the captopril group (82 vs. 52, p = 0.015). This difference was found between 3 and 12 months but not during the first 3 months. After withdrawal from double-blind medication, nine ischemic events were reported in the captopril group compared with one in the placebo group (p = 0.006 between groups).

Conclusions. The present data show that captopril may reduce the incidence of ischemia-related events after MI, which becomes apparent after 3 months. However, no anti-ischemic effect was observed during exercise testing. After withdrawal from ACE inhibition, a high incidence of clinical events occurred, suggesting a rebound phenomenon. (C) 1997 by the American College of Cardiology.