Investigation of therapeutic mechanisms of atenolol and diltiazem in patients with variable-threshold angina

Abstract

The effects of β-adrenoreceptor and calcium channel-blocking agents on the balance of myocardial oxygen supply and demand were studied in 15 patients (2 women and 13 men), aged 46 to 69 (mean 62) years, with variable-threshold angina. An exercise test was performed before therapy was begun, and 24-hour ambulatory ECG monitoring was performed after 1 week of long-acting nitrate therapy, in the third week after random assignment to either atenolol or diltiazem, and in the third week after crossover. All exercise tests were positive except in one patient taking diltiazem. The exercise time to 0.1 mV ST change was 4.2 ± 1.7 minutes with no therapy, 5.1 ± 1.6 minutes with nitrates, 6.6 ± 0.8 minutes with diltiazem, and 6.5 ± 2.1 minutes with atenolol. The rate-pressure product at 0.2 mV ST change was 20.9 ± 4.6 with no therapy and 21.2 ± 5.7 and 22 ± 4.6 with nitrates and diltiazem, respectively, but fell to 15 ± 3.9 beats · min.−1 mm Hg 10−3 after atenolol (p < 0.01). There was no significant difference in the number of anginal attacks or in nitroglycerin consumption per week. The heart rate at the onset of ST-segment change during the exercise test and during ambulatory ECG monitoring was significantly lower during atenolol than during diltiazem treatment. Both atenolol and diltiazem were of similar efficacy in increasing nonischemic exercise duration in patients with variable-threshold angina and acted primarily by slowing the resting heart rate. Atenolol had a more pronounced effect on heart rate, but its effect on angina appeared to be limited by a β2-receptor blockade-induced increase in coronary vascular tone.