Interpretation:

Greater reductions in pulse pressure and central aortic stiffness in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms, and underscore a potential for drug modulation of natriuretic peptides in treatment of hypertension. The vasopeptidase inhibitors like omapatrilat increase natriuretic and vasodilatory peptides including ANP, BNP of myocardial cell origin, C-type NP of endothelial cell origin, bradykinin and adrenomedullin. The sum effect is to block vasoconstriction, enhance vasodilation, and reduce vascular smooth muscle cell proliferation, hypertrophy, and fibrosis. The fact that these agents reduce pulse pressure and aortic stiffness, two factors associated with increased risk for CHF, stroke, and MI, suggest that there may be an advantage to these agents beyond ACEi, but omapatrilat was no better than standard therapy in a recent CHF trial. The clinical trial OPERA is designed to compare omapatrilat to standard therapy for reducing CV events in 12,600 elderly with hypertension and will be completed in about 5 years.