Effects of omapatrilat on systemic arterial function in patients with chronic heart failure

The mechanisms of action of omapatrilat, an agent that inhibits both neutral endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in patients with heart failure have not been previously reported. Forty-eight patients in New York Heart Association functional class II to III, left ventricular ejection fraction less than or equal to 40%, and in sinus rhythm were randomized to a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks. Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0 +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p <0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/- 3.3 mm Hg, p <0.05) pressure were seen after 12 weeks of therapy with higher doses. Ventricular-arterial coupling was im-proved with a dose-related decrease in augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p <0.01); There was no change in resting forearm blood flow between groups; however, maximum forearm vasodilator response during reactive hyperemia increased in the high-dose groups compared with the control group (+266 +43% vs -14 +/- 92%, p <0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (30 +/- 11 vs -2 +/- 7 pmol/L, p <0.01) in high-dose groups consistent with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in ventricular-vascular coupling and arterial function in heart failure. (C) 2001 by Excerpta Medico, Inc.