The potential role of valsartan+AHU377 (LCZ696) in the treatment of heart failure
The potential role of valsartan+AHU377 (LCZ696) in the treatment of heart failure
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DOI：
10.1517/13543784.2013.797963
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发表时间：
2013-08-01
影响因子：
6.1
通讯作者：
van der Meer, Peter
中科院分区：
文献类型：
--
作者：
Voors, Adriaan A.;Dorhout, Bernard;van der Meer, Peter
引言：心力衰竭仍然是一种死亡率极高且生活质量较差的综合征。对于射血分数保留的心力衰竭（HFpEF）患者，尚未有药物显示可改善其死亡率和发病率，因此迫切需要新型药物。LCZ696是一种首创新型血管紧张素受体脑啡肽酶抑制剂（ARNi），可能是一种用于治疗心力衰竭的有趣新药。
涵盖领域：先前的研究表明，一种中性内肽酶和血管紧张素转换酶抑制剂（奥马曲拉）的复方药物在治疗心力衰竭患者方面有良好效果。然而，血管性水肿的发生阻碍了该药物的进一步研发。本文大部分内容将讨论LCZ696的代谢、药代动力学、药效学、临床效果和安全性，尤其关注其在心力衰竭方面的情况。
专家意见：LCZ696在降低血压方面优于单独使用缬沙坦。一项II期试验的初步结果显示，LCZ696比单独使用缬沙坦更能降低N末端B型利钠肽原（NT - proBNP），此外，LCZ696对症状也有有益影响。鉴于这些有希望的初步结果，人们急切期待正在进行的心力衰竭进一步研究的结果。
Introduction: Heart failure remains a syndrome with a very high mortality rate and a poor quality of life. For patients with heart failure and a preserved ejection fraction (HFpEF), no drugs have shown to improve mortality and morbidity, and therefore novel drugs are highly needed. LCZ696, a first in class angiotensin receptor neprilysin inhibitor (ARNi), might be an interesting novel drug for the treatment of heart failure.Areas covered: Previous studies have shown promising effects of a combination drug with a neutral endopeptidase and an angiotensin-converting enzyme inhibitor (omapatrilat) for the treatment of patients with heart failure. However, the occurrence of angioedema prevented the drug from further development. The majority of this paper will discuss the metabolism, pharmacokinetics, pharmacodynamics, clinical effects, and safety of LCZ696, with a particular focus on heart failure.Expert opinion: LCZ696 is superior to valsartan alone in reducing blood pressure. Preliminary results from a Phase II trial showed that LCZ696 reduced NT-proBNP to a greater extent than valsartan alone, and in addition LCZ696 had beneficial effects on symptoms. With these promising first results, the results of ongoing further studies in heart failure are eagerly awaited.