脑啡肽酶抑制剂:心血管治疗领域的新利器

张峰; 王彦欧

doi:10.13201/j.issn.1001-1439.2016.04.023

脑啡肽酶抑制剂:心血管治疗领域的新利器

张峰¹,
王彦欧^2, ,

- 1. 天津市第一中心医院心内科(天津, 300192);
- 2. 天津市第一中心医院健康查体科

详细信息

通讯作者: 王彦欧,E-mail:wyowys@126.com

中图分类号: R541.6

收稿日期: 2015-05-20

Neprilysin inhibition-the new cardiovascular therapeutic weapon

ZHANG Feng¹,
WANG Yanou^2, ,

- Department of Cardiology, Tianjin First Center Hospital, Tianjin 300192, China

More Information

Corresponding author: WANG Yanou, E-mail: wyowys@126.com

Received Date: 20 May 2015

摘要

摘要: 脑啡肽酶抑制剂（又称中性内肽酶抑制剂）是一种新型的，具有潜在改善患者心血管疾病转归的药物。脑啡肽酶抑制剂可增加钠尿肽系统活性，增加尿钠排泄、利尿以及抑制肾素-血管紧张素系统（RAS）的作用。因此，该药对慢性心衰、高血压和慢性肾病的RAS激活状态具有治疗作用。早期的脑啡肽酶抑制剂与血管紧张素转化酶抑制剂结合物由于其无法接受的血管性水肿发生率而终止。然而，新型的血管紧张素受体脑啡肽酶抑制剂——LCZ696，经大量的研究显示对心血管疾病具有有益作用。
- 脑啡肽酶抑制剂 /
- 钠尿肽系统 /
- LCZ696
Abstract: Neprilysin inhibition (NEPi), also known as neutral endopeptidase inhibition, is a new therapeutic strategy with potential to improve outcomes for patients with cardiovascular disease. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin-angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF), hyper-tension and chronic kidney disease. Early NEPi drugs combined with angiotensin converting enzyme inhibitors were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, a new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in cardiovascular disease.
- neprilysin inhibition /
- natriuretic peptide system /
- LCZ696

HTML全文

参考文献(28)

[1]	MANGIAFICO S, COSTELLO-BOERRIGTER L C, ANDERSEN I A, et al. Neutral endopeptidase inhibition and the natriuretic peptide system:an evolving strategy in cardiovascular therapeutics[J]. Eur Heart J, 2013, 34:886-893c.
[2]	CAMPBELL D J. Vasopeptidase inhibition:a double-edged sword?[J]. Hypertension, 2003, 41:383-389.
[3]	ANDO S, RAHMAN M A, BUTLER G C, et al. Comparison of candoxatril and atrial natriureticfactor in healthy men. Effects on hemodynamics, sympathetic activity, heart rate variability, and endothelin[J]. Hypertension, 1995, 26:1160-1166.
[4]	MARTIN F L, STEVENS T L, CATALIOTTI A, et al. Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure[J]. Kidney Int, 2005, 67:1723-1730.
[5]	WEBER M A. Vasopeptidase inhibitors[J]. Lancet, 2001, 358:1525-1532.
[6]	KOSTIS J B, PACKER M, BLACK H R, et al. Omapatrilat and enalapril in patients with hypertension:the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial[J]. Am J Hypertens, 2004, 17:103-111.
[7]	ROULEAU J L, PFEFFER M A, STEWART D J, et al. Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure:IMPRESS randomised trial[J]. Lancet, 2000, 356:615-620.
[8]	PACKER M, CALIFF R M, KONSTAM M A, et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure:the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)[J]. Circulation, 2002, 106:920-926.
[9]	WADA A, OHNISHI M, TSUTAMOTO T, et al. Chronic effects of an endothelin-coverting enzyme inhibitor on cardiorenal and hormonal function in heart failure[J]. Clin Sci (Lond), 2002, 103(Suppl 1):254S-257S.
[10]	NAKAYAMA K, EMOTO N, SUZUKI Y, et al. Physiological relevance of hydrolysis of atrial natriuretic peptide by endothelin-converting enzyme-1[J]. Kobe J Med Sci, 2012, 58:E12-18.
[11]	EMOTO N, RAHARJO S B, ISAKA D, et al. Dual ECE/NEP inhibition on cardiac and neurohumoralfunction during the transition from hypertrophy to heart failure in rats[J]. Hypertension, 2005, 45:1145-1152.
[12]	KALK P, SHARKOVSKA Y, KASHINA E, et al. Endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 prevents hypertensive cardiac remodeling in a blood pressurein-dependent manner[J]. Hypertension, 2011, 57:755-763.
[13]	MELLIN V, JENG A Y, MONTEIL C, et al. Triple ACE-ECE NEP inhibition in heart failure:a com-pareson with ACE and dual ECE-NEP inhibition[J]. J Cardiovasc Pharmacol, 2005, 46:390-397.
[14]	MCMURRAY J J, PACKER M, DESAI A S, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)[J]. Eur J Heart Fail, 2013, 15:1062-1073.
[15]	GU J, NOE A, CHANDRA P, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor(ARNi)[J]. J Clin Pharmacol, 2010, 50:401-414.
[16]	RUILOPE L, DUKAT A, BÖHM M, et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin:a randomised, double-blind, placebo-controlled, active comparator study[J]. Lancet, 2010, 375:1255-1266.
[17]	KARIO K, SUN N, CHIANG F T, et al. Efficacy and safety of LCZ696, afirst-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension:a randomized, double-blind, placebo-controlled study[J]. Hypertension, 2014, 63:698-705.
[18]	WILLIAMS B, COCKCROFT J R, KARIO K, et al. Rationale and study design of the prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker measuring arterial stiffness in the elderly (PARAMETER) study[J]. BMJ Open, 2014, 4:e004254.
[19]	ITO S, SATOH M, TAMAKI Y, et al. Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction[J]. Hypertens Res, 2015, Feb 19, doi:10.1038/hr.2015.1.
[20]	SOLOMON S D, ZILE M, PIESKE B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction:a phase 2 double-blind randomised controlled trial[J]. Lancet, 2012, 380:1387-1395.
[21]	JHUND P S, CLAGGETT B L, VOORS A A, et al. Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696[J]. Circ Heart Fail, 2014, 7:953-959.
[22]	MCMURRAY J J, PACKER M, DESAI A S, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)[J]. Eur J Heart Fail, 2013, 15:1062-1073.
[23]	MCMURRAY J J, PACKER M, DESAI A S, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure[J]. N Engl J Med, 2014, 371:993-1004.
[24]	VARDENY O, MILLER R, SOLOMON S D. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure[J]. JACC Heart Fail, 2014, 2:663-670.
[25]	PACKER M, MCMURRAY J J, DESAI A S, et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure[J]. Circulation, 2015, 131:54-61.
[26]	VARDENY O, TACHENY T, SOLOMON S D. First-in-class angiotensin receptor neprilysin inhibitor in heart failure[J]. Clin Pharmacol Ther, 2013, 94:445-448.
[27]	VOORS A A, GORI M, LIU L C, et al. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction[J]. Eur J Heart Fail, 2015, 17:510-517
[28]	JUDGE P, HAYNES R, LANDRAY M J, et al. Neprilysin inhibition in chronic kidney disease[J]. Nephrol Dial Transplant, 2014, 18:1-6.