open access

Vol 23, No 6 (2016)
CLINICAL CARDIOLOGY - REVIEW ARTICLE
Published online: 2016-09-13
Get Citation

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Erik H. Howell, Scott J. Cameron
DOI: 10.5603/CJ.a2016.0063
·
Pubmed: 27665860
·
Cardiol J 2016;23(6):591-598.

open access

Vol 23, No 6 (2016)
CLINICAL CARDIOLOGY - REVIEW ARTICLE
Published online: 2016-09-13

Abstract

Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta-adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality.

Abstract

Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta-adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality.

Get Citation

Keywords

neprilysin; sacubitril; valsartan endopeptidase; heart failure; cardiomyopathy; LCZ696

About this article
Title

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Journal

Cardiology Journal

Issue

Vol 23, No 6 (2016)

Pages

591-598

Published online

2016-09-13

DOI

10.5603/CJ.a2016.0063

Pubmed

27665860

Bibliographic record

Cardiol J 2016;23(6):591-598.

Keywords

neprilysin
sacubitril
valsartan endopeptidase
heart failure
cardiomyopathy
LCZ696

Authors

Erik H. Howell
Scott J. Cameron

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl