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The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond

  • Hypertension (DS Geller and DL Cohen, Section Editors)
  • Published:
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Abstract

Purpose of Review

Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT1) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF). In addition, sacubitril/valsartan has been developed for the management of hypertension, because it has unique anti-aging properties. However, the clinical evidence of mechanism has not been well validated.

Recent Findings

A recent mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is superior to angiotensin receptor blocker (ARB) monotherapy for reducing central aortic systolic pressure (primary endpoint) as well as for central aortic pulse pressure (secondary endpoint) and nocturnal BP preferentially.

Summary

Considering these results, sacubitril/valsartan may be an attractive therapeutic agent to treat the elderly with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension characterized as systolic (central) hypertension (structural hypertension) and/or nocturnal hypertension (salt-sensitive hypertension). These are the high-risk hypertension phenotypes which are prone to develop heart failure with preserved EF and chronic kidney disease. Sacubitril/valsartan may be effective to suppress the age-related continuum from hypertension to heart failure, and it could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients.

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Acknowledgements

The author would like to thank Mrs. Ayako Okura, Department of Cardiovascular Medicine, Jichi Medical University School of Medicine, for her editorial support.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine (JMU), JMU Center of Excellence, Community Medicine Cardiovascular Research and Development (JCARD), Jichi, Japan

    Kazuomi Kario

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Correspondence to Kazuomi Kario.

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Conflict of Interest

Kazuomi Kario has received honoraria from Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Omron Healthcare Co., Ltd., Bayer Yakuhin Ltd., Mochida Pharmaceutical Co., Ltd, and Sumitomo Dainippon Pharma Co., Ltd. He has also received research grants from Teijin Pharma Limited, Omron Healthcare Co., Ltd., Fukuda Denshi Co., Ltd., Bayer Yakuhin Co., Ltd., A&D Co. Ltd., Daiichi Sankyo Co., Ltd., Mochida Pharmaceutical Co., Ltd., EA Pharma, Boehringer Ingelheim Japan Inc., Tanabe Mitsubishi Pharma Corporation, Shionogi & Co., Ltd., Terumo Corporation, MSD K.K, Sanwa Kagaku Kenkyusho Co., Ltd., Bristol-Myers Squibb K.K, and Otsuka Pharmaceutical Co., Ltd.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This article is part of the Topical Collection on Hypertension

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Kario, K. The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond. Curr Cardiol Rep 20, 5 (2018). https://doi.org/10.1007/s11886-018-0944-4

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