PDF(Pubmed)
Abstract：
This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation of the angiotensin system. ARNi therapy is very effective in reducing the risks of death and hospitalization for HF in patients with HF and New York Heart Association functional class II to III symptoms, but studies failed to show any benefits with ARNi when compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker in patients with advanced HF with reduced ejection fraction or in patients following myocardial infarction with left ventricular dysfunction but without HF. These raise the questions about whether the enzymatic breakdown of natriuretic peptides may not be a very effective solution in advanced HF patients when there is downstream blunting of the response to natriuretic peptides or among post-myocardial infarction patients in the absence of HF when there may not be a need for increased natriuretic peptide availability. Furthermore, there is a need for additional studies to determine the long-term effects of ARNi on albuminuria, obesity, glycemic control and lipid profile, blood pressure, and cognitive function in patients with HF.
摘要：
本文在最近的临床试验的背景下，提供了关于脑啡肽抑制在心力衰竭（HF）中的作用的当代综述和新观点，并解决了某些HF患者人群的潜在机制和未解决的问题。Neprilysin是一种内肽酶，可切割多种肽，例如利钠肽，缓激肽,肾上腺髓质素,P物质,血管紧张素I和II，和内皮素。它对心血管有广泛的作用，肾,肺,胃肠,内分泌，和神经功能。已经开发了联合的血管紧张素受体和脑啡肽抑制剂（ARNi），旨在增加血管舒张利钠肽并防止血管紧张素系统的反调节激活。ARNi治疗对于降低HF和纽约心脏协会功能II至III类症状患者的死亡和住院风险非常有效。但与血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂相比,研究未能显示ARNi在射血分数降低的晚期HF患者或伴有左心室功能障碍但无HF的心肌梗死患者中的任何益处.这些提出了以下问题：当存在对利钠肽的反应的下游钝化时，利钠肽的酶促分解在晚期HF患者中或在不存在HF的心肌梗死后患者中是否可能不是非常有效的解决方案需要增加利钠肽的可用性。此外，需要进一步的研究来确定ARNi对蛋白尿的长期影响，肥胖，血糖控制和血脂，血压,HF患者的认知功能。
