Clinical, electrocardiographic, and hemodynamic effects of ICI 89,406, a new cardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, in patients with angina pectoris.

ICI 89,406, a new cardioselective beta-adrenoceptor antagonist possessing marked intrinsic sympathomimetic activity, was administered (0.04 mg/kg, i.v.) to 10 patients with stable, uncomplicated, exercise-induced angina pectoris and angiographically proven coronary artery disease. The drug resulted in a significant reduction in heart rate (from 125 +/- 5 to 110 +/- 4/min, p less than 0.001), mean systemic arterial pressure (from 147 +/- 4 to 137 +/- 3 mm Hg, p less than 0.01), and electrocardiographic ST-segment depression (from 1.9 +/- 0.5 to 0.8 +/- 0.3 mm, p less than 0.01) without any change in pulmonary arterial or wedge pressure during submaximal supine leg exercise on a bicycle ergometer. These changes were accompanied by a reduction of cardiac output in 6/10 patients and of the duration of pain in 8/10 patients. At rest, all the hemodynamic parameters remained essentially unchanged in comparison with the control study. These studies indicate that ICI 89,406 produces effective beta-adrenoceptor blockade during exercise in patients with angina pectoris. The partial agonist activity of the drug may be responsible for the minimal circulatory response at rest.