This is a multicenter, randomized, double-blind trial to evaluate the hemodynamic effects, safety and tolerability of BMS-186716 after a single oral dose and after 12-weeks of once-daily oral therapy in subjects with heart failure (NYHA Class II-IV and resting LVEF,/-40%). BMS-186716 is a novel dual-metalloprotease inhibitor providing selective inhibition of neutral endopeptidase (NEP) and angiotensin converting enzyme (AC). Inhibition of NEP and ACE prevents the enzymatic degradation of atrial natriuretic peptide and brain natriuretic peptide thereby potentiating the intrinsic diuretic, natriuretic, vasodilatory and anti-proliferative actions of these endogenous vasoactive proteins. NEP and ACE also play a role in the hydrolysis of bradykinins resulting in vasodilation, increased renal bloodflow and improved natriuresis. This dual inhibition is postulated to therefore improve the hemodynamic functioning of the failing heart through pre- and after-load reduction leading to improvements in functional status in subjects with heart failure.
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