HEMODYNAMIC EFFECTS & SAFETY OF DUAL METALLOPROTEASE BMS186716 IN HEART FAILURE

这是一项多中心、随机、双盲试验，目的是评估心力衰竭患者在单次口服和每日一次口服治疗12周后(纽约心脏协会II-IV级和静息左心室射血分数，/-40%)服用BMS-186716的血流动力学效应、安全性和耐受性。BMS-186716是一种新型的双金属蛋白酶抑制剂，可选择性抑制中性内肽酶和血管紧张素转换酶。抑制NEP和ACE可阻止心钠素和脑钠素的酶降解，从而增强这些内源性血管活性蛋白的内源性利尿、利钠、血管扩张和抗增殖作用。NEP和ACE也在缓激肽的水解中发挥作用，从而导致血管扩张、增加肾脏血流量和改善钠尿。这种双重抑制被认为可以通过前后负荷的减少来改善衰竭心脏的血流动力学功能，从而改善心力衰竭受试者的功能状态。

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.