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World J Cardiol. Aug 26, 2021; 13(8): 325-339
Published online Aug 26, 2021. doi: 10.4330/wjc.v13.i8.325
Angiotensin receptor blocker neprilysin inhibitors
Daisuke Usuda, Toshihiro Higashikawa, Yuta Hotchi, Kenki Usami, Shintaro Shimozawa, Shungo Tokunaga, Ippei Osugi, Risa Katou, Sakurako Ito, Toshihiko Yoshizawa, Suguru Asako, Kentaro Mishima, Akihiko Kondo, Keiko Mizuno, Hiroki Takami, Takayuki Komatsu, Jiro Oba, Tomohisa Nomura, Manabu Sugita
Daisuke Usuda, Yuta Hotchi, Kenki Usami, Shintaro Shimozawa, Shungo Tokunaga, Ippei Osugi, Risa Katou, Sakurako Ito, Toshihiko Yoshizawa, Suguru Asako, Kentaro Mishima, Akihiko Kondo, Keiko Mizuno, Hiroki Takami, Takayuki Komatsu, Jiro Oba, Tomohisa Nomura, Manabu Sugita, Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Nerima-ku 177-8521, Tokyo, Japan
Toshihiro Higashikawa, Geriatric Medicine, Kanazawa Medical University Himi Municipal Hospital, Himi-shi 935-8531, Toyama, Japan
Author contributions: Usuda D wrote the manuscript; Higashikawa T, Hotchi Y, Usami K, Shimozawa S, Tokunaga S, Osugi I, Katou R, Ito S, Yoshizawa T, Asako S, Mishima K, Kondo A, Mizuno K, Takami H, Komatsu T, Oba J, Nomura T, and Sugita M proofread and revised the manuscript; all authors approved the final version to be published.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Daisuke Usuda, MD, MSc, PhD, Doctor, Lecturer, Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, 3-1-10, Takanodai, Nerima-ku 177-8521, Tokyo, Japan. d.usuda.qa@juntendo.ac.jp
Received: March 18, 2021
Peer-review started: March 18, 2021
First decision: June 7, 2021
Revised: June 9, 2021
Accepted: July 26, 2021
Article in press: July 26, 2021
Published online: August 26, 2021
Processing time: 158 Days and 10.4 Hours
Abstract

Heart failure (HF) is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with, or eject, blood. It is a multifaceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. Regarding the mechanism of HF, three neurohumoral factors - the renin-angiotensin-aldosterone system, the sympathetic nervous system, and natriuretic peptides — are related to the pathology of chronic HF (CHF), and the targets of treatment. Angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), has been introduced as a treatment for CHF. SAC/VAL is an efficacious, safe, and cost-effective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction (HFrEF), and reduces hospital admissions. An in-hospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL. In the last five years, SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF. On the other hand, further work, with carefully designed and controlled preclinical studies, is necessary for understanding the molecular mechanisms, effects, and confirmation of issues such as long-term safety in both human and animal models.

Keywords: Angiotensin receptor blocker and neprilysin inhibitor; Chronic heart failure; Renin-angiotensin-aldosterone-system; Sympathetic nervous system; Natriuretic peptide; Sacubitril/valsartan

Core Tip: Heart failure (HF) is a multi-faceted clinical condition that affects up to 2% of the population in the developed world, and is linked to significant morbidity and mortality; it is therefore considered a major concern for public health. In 2014, a newly developed angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor), namely sacubitril/valsartan (SAC/VAL), was introduced as a treatment for chronic HF (CHF), and it proved to have the efficacy, safety, and cost-effectiveness to improve quality of life and longevity in patients with heart failure with reduced ejection fraction and reduces hospital admission. In this review, we first summarize the current knowledge regarding HF, then provide an overview of the current knowledge on SAC/VAL for CHF, together with relevant clinical trials and future perspectives.