EFFECTS OF BENAZEPRIL AND METOPROLOL OROS ALONE AND IN COMBINATION ON MYOCARDIAL-ISCHEMIA IN PATIENTS WITH CHRONIC STABLE ANGINA

The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (±SEM) exercise time was 8.5 ± 0.7 min with placebo, 8.3 ± 0.6 min (95% confidence interval [CI] −1.06 to 0.54) with benazepril, 9.4 ± 0.5 min (95% CI −0.32 to 2.14) with metoprolol OROS and 9.6 ± 0.5 min (95% CI −0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 ± 0.6 min with placebo to 6.3 ± 0.6 min (95% CI −0.93 to 1.45) with benazepril, 7.9 ± 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 ± 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignifi-cantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product. During ambulatory ECG monitoring, heart rate was lowered throughout the 24 h period with metoprolol OROS but not with benazepril. Total episodes of ST segment depression in 24 h were 221 with placebo, 160 (95% CI −3.72 to 1.28) with benazepril, 136 (95% CI −4.68 to −0.89) with metoprolol OROS and 150 (95% CI −5.35 to 0.78) with the combination of benazepril and metoprolol OROS. Similarly, total ischemic burden was 1,549 min with placebo, which was reduced to 879 min (95% CI −48.28 to 1.92) with benazepril, 807 min (95% CI −44.87 to −6.63) with metoprolol OROS and 828 min (95% CI −49.63 to −0.37) with the combination of these. In conclusion, metoprolol OROS is an effective antiischemic agent. Benazepril did not produce any clinical benefit in terms of exercise test variables. However, a clinically meaningful although statistically nonsignificant reduction in severity and number of ischemic episodes and duration of ST segment depression during ambulatory ST segment monitoring was observed. Because about 97% of ischemic episodes were silent, the findings suggest that benazepril might be beneficial in improving silent myocardial ischemia. Both drugs were well tolerated when administered singly or together. The data also confirm that benazepril did not impair the anti-ischemic effects of metoprolol OROS. © 1990, American College of Cardiology Foundation. All rights reserved.