Complementary Mechanisms of Atenolol and Diltiazem in the Clinical Improvement of Patients with Stable Angina

Abstract

The combination of atenolol with diltiazem has been shown to be useful in the treatment of patients with coronary artery disease. Eighteen patients with proven coronary artery disease, stable angina, and no previous myocardial in farction were studied before and after treatment with atenolol (100 mg/day) (9 patients) or diltiazem (180 mg/day) (9 patients). Ischemic threshold at stress test, pressure-rate product at ischemic threshold, direct oxygen consumption at ischemic threshold, and exercise ejection fraction were determined.

There was a slight increase in the duration of exercise, maximal oxygen con sumption, and ischemic threshold after treatment with each drug. Double prod uct at ischemic threshold decreased from 20.9 to 19.8 (p = NS) with atenolol but increased from 20.1 to 21.9 (p=NS) with diltiazem. Conversely oxygen con sumption at ischemic threshold increased with atenolol to nearly significant val ues from 17.2 to 23.6 (p = 0.067) but not with diltiazem (16.2 to 22.3; p = 0.16) .

Before treatment, exercise ejection fraction increased less than 10% or de creased from its resting values in all patients but 1 with atenolol and 1 with diltiazem, but exercise ejection fraction increased significantly after treatment with atenolol (60.6 to 67.5; p=0.02) but not with diltiazem. This improvement was due to a significant reduction in end systolic volume (103.8 to 78.6; p=0.019), despite a similar increase in heart rate and blood pressure in all patients.

There was a trend to increase ischemic threshold with both drugs that could have been produced by: (1) atenolol, by increasing oxygen consumption at the ischemic threshold, which suggests an improvement in ventricular perform ance; (2) diltiazem, by increasing double product at the ischemic threshold, which reflects an increase in myocardial oxygen consumption at the ischemic threshold and suggests a parallel improvement in myocardial flow. Atenolol produces a significant increase in exercise ejection fraction owing to a reduction in end systolic volume. This finding suggests a protective effect of atenolol in exercise-induced ischemia and agrees with the trends observed in stress tests.