The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan.
The neprilysin pathway in heart failure: a review and guide on the use of sacubitril/valsartan.
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DOI：
10.1136/heartjnl-2014-306775
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发表时间：
2016-09-01
期刊：
影响因子：
--
通讯作者：
McMurray JJ
中科院分区：
文献类型：
--
作者：
Jhund PS;McMurray JJ
抑制神经体液通路如肾素血管紧张素醛固酮和交感神经系统是理解和治疗心力衰竭（HF）的核心。相反，直到最近，潜在的有益的神经体液系统的增强，如利钠肽已经有限的治疗成功。给予合成利钠肽并没有改善急性HF的结局，但通过抑制降解利钠肽（和其他血管活性）肽的酶脑啡肽酶来调节利钠系统已被证明是成功的。在脑啡肽酶单独抑制或脑啡肽酶-血管紧张素转换酶（ACE）双重抑制最初失败后，血管紧张素受体脑啡肽酶抑制剂（ARNI）与ACEI的前瞻性比较以确定心力衰竭试验（PARADIGM-HF）中全球死亡率和发病率的影响，该试验表明，血管紧张素受体阻滞剂脑啡肽酶抑制剂沙库巴曲/缬沙坦（以前的LCZ 696）可改善发病率和死亡率。与ACE抑制剂依那普利相比，沙库巴曲/缬沙坦使主要终点（心血管死亡或因HF住院）的发生率降低20%，全因死亡率降低16%。这些结果表明，沙库巴曲/缬沙坦应取代ACE抑制剂或血管紧张素受体阻滞剂作为治疗HF和射血分数降低的症状性患者（NYHA II-IV级）的基础。本综述将探讨心力衰竭中脑啡肽酶抑制的背景，PARADIGM-HF试验的结果，并为如何在临床实践中使用沙库巴曲/缬沙坦提供指导。
Inhibition of neurohumoural pathways such as the renin angiotensin aldosterone and sympathetic nervous systems is central to the understanding and treatment of heart failure (HF). Conversely, until recently, potentially beneficial augmentation of neurohumoural systems such as the natriuretic peptides has had limited therapeutic success. Administration of synthetic natriuretic peptides has not improved outcomes in acute HF but modulation of the natriuretic system through inhibition of the enzyme that degrades natriuretic (and other vasoactive) peptides, neprilysin, has proven to be successful. After initial failures with neprilysin inhibition alone or dual neprilysin-angiotensin converting enzyme (ACE) inhibition, the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) trial demonstrated that morbidity and mortality can be improved with the angiotensin receptor blocker neprilysin inhibitor sacubitril/valsartan (formerly LCZ696). In comparison to the ACE inhibitor enalapril, sacubitril/valsartan reduced the occurrence of the primary end point (cardiovascular death or hospitalisation for HF) by 20% with a 16% reduction in all-cause mortality. These findings suggest that sacubitril/valsartan should replace an ACE inhibitor or angiotensin receptor blocker as the foundation of treatment of symptomatic patients (NYHA II–IV) with HF and a reduced ejection fraction. This review will explore the background to neprilysin inhibition in HF, the results of the PARADIGM-HF trial and offer guidance on how to use sacubitril/valsartan in clinical practice.
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