The clinical, cardiac, renal, arterial and neurohormonal effects of omapatrilat, a vasopeptidase inhibitor, in patients with chronic heart failure

OBJECTIVES We sought to examine the effects of long-term vasopeptidase inhi bition in patients with heart failure. BACKGROUND The long-term effects of omapatrilat, an agent that inhibits bot h neutral endopeptidase and angiotensin-converting enzyme, on clinical stat us, neurohormonal indexes and left ventricular function in patients with ch ronic heart failure (CHF) have not been previously documented. METHODS Forty-eight patients in New York Heart Association functional class II or III, with left ventricular ejection fraction (LVEF) less than or equ al to 40% and in sinus rhythm were randomized to a dose-ranging pilot study of omapatrilat for 12 weeks. Measurements were performed at baseline and 1 2 weeks. RESULTS There was an improvement in functional status, as reported by the p atient (p < 0.001) and physician (p < 0.001) at 12 weeks. Dose-dependent im provements in LVEF (p < 0.001) and LV end-systolic wall stress (sigma) (p < 0.05) were seen, together with a reduction in systolic blood pressure (p < 0.05). There was evidence of a natriuretic effect (p < 0.001), and total b lood volume decreased (p < 0.05). Omapatrilat induced an increase in postdo se plasma atrial natriuretic peptide levels (p < 0.01) in the high dose gro ups, with a reduction in predose plasma brain natriuretic peptide (p < 0.00 1) and epinephrine (p < 0.01) levels after 12 weeks of therapy. Omapatrilat was well tolerated. CONCLUSIONS The sustained hemodynamic, neurohumoral and renal effects of om apatrilat, together with improved functional status, suggest that vasopepti dase inhibition has potential as a new therapeutic modality for the treatme nt of CHF. (C) 2000 by the American College of Cardiology.