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Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date

Authors Vilela-Martin JF

Received 10 January 2016

Accepted for publication 5 April 2016

Published 9 May 2016 Volume 2016:10 Pages 1627—1639

DOI https://doi.org/10.2147/DDDT.S84782

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


José Fernando Vilela-Martin

Internal Medicine Department, São José do Rio Preto State Medical School (FAMERP), São José do Rio Preto, Brazil

Abstract: Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin–angiotensin–aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Keywords: heart failure, vasopeptidase, natriuretic peptides, neprilysin, sacubitril, valsartan

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