HEMODYNAMIC EFFECTS & SAFETY OF DUAL METALLOPROTEASE BMS186716 IN HEART FAILURE

这是一项多中心、随机、双盲试验，旨在评估 BMS-186716单次给药对血流动力学的影响及安全性和耐受性 口服剂量和每日一次口服治疗12周后 心力衰竭(NYHA II-IV级和静息左心室射血分数，/-40%)。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(NEP)和血管紧张素转换酶(Ac)。 抑制NEP和ACE可阻止心房的酶降解 利钠肽和脑利钠肽，从而增强 内源性利尿、利钠、血管扩张和抗增殖作用 这些内源性血管活性蛋白的作用。NEP和Ace也扮演着 在缓激肽的水解中的作用，导致血管扩张，增加 肾血流量和改善的尿钠。这种双重抑制是 因此被认为可以改善衰竭患者的血流动力学功能 通过减少前后负荷来改善心脏功能 心力衰竭患者的功能状态。

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 blood flow 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.