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

Abstract

Objectives: We sought to examine the effects of long-term vasopeptidase inhibition in patients with heart failure.

Background: The long-term effects of omapatrilat, an agent that inhibits both neutral endopeptidase and angiotensin-converting enzyme, on clinical status, neurohormonal indexes and left ventricular function in patients with chronic 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)< or =40% and in sinus rhythm were randomized to a dose-ranging pilot study of omapatrilat for 12 weeks. Measurements were performed at baseline and 12 weeks.

Results: There was an improvement in functional status, as reported by the patient (p<0.001) and physician (p<0.001) at 12 weeks. Dose-dependent improvements 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 blood volume decreased (p<0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (p<0.01) in the high dose groups, with a reduction in predose plasma brain natriuretic peptide (p<0.001) and epinephrine (p<0.01) levels after 12 weeks of therapy. Omapatrilat was well tolerated.

Conclusions: The sustained hemodynamic, neurohumoral and renal effects of omapatrilat, together with improved functional status, suggest that vasopeptidase inhibition has potential as a new therapeutic modality for the treatment of CHF.