HEMODYNAMIC AND HORMONAL EFFECTS OF QUINAPRILAT IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Objective: To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with pl acebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both. Methods: Patients were randomly assigned to three tre atment groups to receive low (0.5 and 1.0 mg), medium (1.0 and 2.5 mg) , or high (5.0 and 10.0 mg) single intravenous doses of quinaprilat or placebo on day I, On the basis of responses observed on day 1, the th ree treatment groups received stable multiple intravenous doses of eit her quinaprilat or placebo every 6 hours on days 2 and 3, Hemodynamic measurements, hormonal assessments, and safety were evaluated before a nd at specified intervals during the study, Results: Compared with pla cebo, single and multiple doses of quinaprilat increased cardiac index and reduced pulmonary capillary wedge pressure, mean arterial pressur e, systemic vascular resistance, and right atrial pressure in a dose-r elated manner, No clinically important change in heart rate was abserv ed. Hemodynamic changes after multiple-dose quinaprilat administration were similar to those observed after single doses and were generally sustained during the 6-hour dosing interval, Relative to placebo, quin aprilat reduced plasma angiotensin converting enzyme (ACE) activity, a ngiotensin II concentration, and aldosterone concentration and increas ed plasma renin activity; no prominent changes in plasma catecholamine and atrial natriuretic peptide concentrations were observed. There we re no clinically important drug-related changes in the safety paramete rs, Conclusions; Single and multiple intravenous doses of 0.5 to 10 mg quinaprilat are well-tolerated and produce favorable dose-dependent h emodynamic effects and hormonal changes consistent mil those expected of an ACE inhibitor in patients with NYHA class III and IV congestive heart failure.