Combined Neprilysin and Renin-Angiotensin System Inhibition for the Treatment of Heart Failure
Combined Neprilysin and Renin-Angiotensin System Inhibition for the Treatment of Heart Failure
复制标题
DOI：
10.1016/j.jchf.2014.09.001
复制
发表时间：
2014-12-01
影响因子：
13
通讯作者：
Solomon, Scott D.
中科院分区：
文献类型：
--
作者：
Vardeny, Orly;Miller, Ryan;Solomon, Scott D.
脑啡肽溶酶是一种有助于分解生物活性利钠肽和其他几种血管活性化合物的酶。抑制脑啡肽酶已经成为几种化合物的治疗靶点，这些化合物已经在心血管疾病中进行了测试，包括ecadotril，candoxatril，omapatrilat和LCZ 696。虽然ecadotril，candoxatril和omapatrilat最初在高血压和/或心力衰竭中进行了测试，但缺乏疗效和副作用导致其开发停止。LCZ 696（沙库巴曲缬沙坦）是一种一流的血管紧张素受体脑啡肽酶抑制剂，已开发用于心力衰竭。该化合物由2个分子组成的单晶复合物-血管紧张素受体阻滞剂缬沙坦和脑啡肽酶抑制剂前体药物-现在已经在高血压中进行了测试，在射血分数保留的心力衰竭的2期试验中，并且在射血分数降低的心力衰竭的3期试验中表现出比依那普利更大的疗效。其抑制肾素-血管紧张素-醛固酮轴和增强内源性利钠肽系统的能力为心血管疾病提供了独特的作用机制。(C)2014年由美国心脏病学会基金会。
Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696. Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 (sacubitril valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that has been developed for use in heart failure. This compound is composed of 2 molecular moieties in a single crystalline complex-the angiotensin receptor blocker valsartan and a neprilysin inhibitor prodrug-and has now been tested in hypertension, in a phase 2 trial in heart failure with preserved ejection fraction, and has demonstrated greater efficacy than enalapril in a phase 3 trial in heart failure with reduced ejection fraction. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. (C) 2014 by the American College of Cardiology Foundation.