A haemodynamic dose finding study with a new slow-calcium channel blocker (amlodipine) in coronary artery disease.

The haemodynamic dose-response effects of a new long-acting slow-calcium channel blocking agent, amlodipine were evaluated in 20 patients with angiographically confirmed coronary heart disease. At rest, following a control saline period, four i.v. doses of the drug (cumulative dosage 1.25, 2.5, 5 and 10 mg) were administered to ten patients and haemodynamics determined in the ten to 15 minutes following injection. Effects on circulatory parameters were only evident following the maximum cumulative dosage. Accordingly in a further ten patients, the regimen was doubled (cumulative i.v. dosage 2.5, 5, 10 and 20 mg). In each study the haemodynamic effects during constant load supine bicycle exercise were evaluated by comparison of values during the control exercise period and following the final cumulative dosage. On the higher regimen, amlodipine significantly reduced resting systolic, diastolic and mean (p less than 0.01) systemic arterial pressure and systemic vascular resistance index (p less than 0.01). Heart rate (p less than 0.01), stroke volume index (p less than 0.01) and cardiac index (p less than 0.01) increased; pulmonary artery occluded pressure was unchanged. During constant load bicycle exercise, the mean arterial pressure was significantly reduced (p less than 0.01), and the heart rate and cardiac index increased (p less than 0.01). Thus the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and augment cardiac pumping performance. The minimum effective i.v. dosage appeared to be 10 mg. Amlodipine appears sufficiently promising to warrant longer-term studies in ischaemic heart disease.