Effects of omapatrilat on hemodynamics and safety in patients with heart failure

Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and select ive inhibitor of neutral endopeptidase and angiotensin-converting enzyme; i ts therapeutic potential is being investigated for treatment of hypertensio n and heart failure. In the present study, the safety, tolerability, and he modynamic effects of single oral doses of omapatrilat (1 to 50 mg) are comp ared with placebo in patients with heart failure. Patients with heart failu re (New York Heart Association functional class II to IV) and a resting lef t ventricular ejection fraction less than or equal to 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic asse ssment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wed ge pressure by approximate to6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared w ith placebo with an approximate to2.5-mm Hg reduction in mean pulmonary cap illary wedge pressure at 24 hours. Omapatrilat improved additional hemodyna mic parameters, including cardiac index, systemic vascular resistance, stro ke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from basel ine in plasma atrial natriuretic peptide (twofold) and cyclic guanosine mon ophosphate (nearly twofold) was observed. Moreover, omapatrilat was well to lerated. Thus, omapatrilat administered orally to patients with heart failu re was safe and well tolerated and resulted in improved hemodynamic perform ance. (C) 2001 by Excerpta Medical, Inc.