Document Detail


Combined Neprilysin and Renin-Angiotensin System Inhibition for the Treatment of Heart Failure.
MedLine Citation:
PMID:  25306450     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Orly Vardeny; Ryan Miller; Scott D Solomon
Publication Detail:
Type:  REVIEW     Date:  2014-9-27
Journal Detail:
Title:  JACC. Heart failure     Volume:  -     ISSN:  2213-1787     ISO Abbreviation:  JACC Heart Fail     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-10-12     Completed Date:  -     Revised Date:  2014-10-13    
Medline Journal Info:
Nlm Unique ID:  101598241     Medline TA:  JACC Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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