Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10165110 | JACC: Heart Failure | 2014 | 7 Pages |
Abstract
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.
Keywords
ANPACECNPBNPHFpEFLVEFNYHANT-proBNPHFrEFAngiotensin-converting enzymeNew York Heart Associationconfidence intervalHeart failure with preserved ejection fractionheart failureheart failure with reduced ejection fractionhazard ratioNeprilysinNatriuretic peptideC-type natriuretic peptideatrial natriuretic peptideleft ventricular ejection fraction
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Authors
Orly PharmD, MS, Ryan BS, Scott D. MD,