Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade

OBJECTIVES We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. BACKGROUND Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. METHODS We studied 43 patients (average age 63 ± 8 years) with exercise-induced myocardial ischemia (≥0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term). RESULTS At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate × systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 ± 1.9 min) but was unchanged in the placebo group (4.4 ± 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS). CONCLUSIONS Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.