Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review

Heart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathoph...

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Autores principales:	Domingo Pascual-Figal, Antoni Bayés-Genis, Paola Beltrán-Troncoso, Pedro Caravaca-Pérez, Alicia Conde-Martel, Maria G. Crespo-Leiro, Juan F. Delgado, Javier Díez, Francesc Formiga, Nicolás Manito
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	heart failure heart failure with reduced ejection fraction sacubitril/valsartan ARNI neprilysin inhibition Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/367a0118f2f647ed9ac35f91293314da
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spelling	oai:doaj.org-article:367a0118f2f647ed9ac35f91293314da2021-11-11T06:05:40ZSacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review2297-055X10.3389/fcvm.2021.754499https://doaj.org/article/367a0118f2f647ed9ac35f91293314da2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.754499/fullhttps://doaj.org/toc/2297-055XHeart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathophysiology of HF. First, the renin-angiotensin-aldosterone system (RAAS) is over-activated, causing vasoconstriction, hypertension, elevated aldosterone levels and sympathetic tone, and eventually cardiac remodeling. Second, an endogenous compensatory mechanism, the natriuretic peptide (NP) system is also activated, albeit insufficiently to counteract the RAAS effects. Since NPs are degraded by the enzyme neprilysin, it was hypothesized that its inhibition could be an important therapeutic target in HF. Sacubitril/valsartan is the first of the class of dual neprilysin and angiotensin receptor inhibitors (ARNI). In patients with HFrEF, treatment with sacubitril/valsartan has demonstrated to significantly reduce mortality and the rates of hospitalization and rehospitalization for HF when compared to enalapril. This communication reviews in detail the demonstrated benefits of sacubitril/valsartan in the treatment of patients with HFrEF, including reduction of mortality and disease progression as well as improvement in cardiac remodeling and quality of life. The hemodynamic and organic effects arising from its dual mechanism of action, including the impact of neprilysin inhibition at the renal level, especially relevant in patients with type 2 diabetes mellitus, are also reviewed. Finally, the evidence on the demonstrated safety and tolerability profile of sacubitril/valsartan in the different subpopulations studied has been compiled. The review of this evidence, together with the recommendations of the latest clinical guidelines, position sacubitril/valsartan as a fundamental pillar in the treatment of patients with HFrEF.Domingo Pascual-FigalDomingo Pascual-FigalAntoni Bayés-GenisAntoni Bayés-GenisAntoni Bayés-GenisPaola Beltrán-TroncosoPedro Caravaca-PérezPedro Caravaca-PérezPedro Caravaca-PérezAlicia Conde-MartelMaria G. Crespo-LeiroMaria G. Crespo-LeiroJuan F. DelgadoJuan F. DelgadoJuan F. DelgadoJavier DíezJavier DíezJavier DíezJavier DíezFrancesc FormigaNicolás ManitoFrontiers Media S.A.articleheart failureheart failure with reduced ejection fractionsacubitril/valsartanARNIneprilysin inhibitionDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heart failure heart failure with reduced ejection fraction sacubitril/valsartan ARNI neprilysin inhibition Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	heart failure heart failure with reduced ejection fraction sacubitril/valsartan ARNI neprilysin inhibition Diseases of the circulatory (Cardiovascular) system RC666-701 Domingo Pascual-Figal Domingo Pascual-Figal Antoni Bayés-Genis Antoni Bayés-Genis Antoni Bayés-Genis Paola Beltrán-Troncoso Pedro Caravaca-Pérez Pedro Caravaca-Pérez Pedro Caravaca-Pérez Alicia Conde-Martel Maria G. Crespo-Leiro Maria G. Crespo-Leiro Juan F. Delgado Juan F. Delgado Juan F. Delgado Javier Díez Javier Díez Javier Díez Javier Díez Francesc Formiga Nicolás Manito Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
description	Heart failure (HF) is a clinical syndrome characterized by the presence of dyspnea or limited exertion due to impaired cardiac ventricular filling and/or blood ejection. Because of its high prevalence, it is a major health and economic burden worldwide. Several mechanisms are involved in the pathophysiology of HF. First, the renin-angiotensin-aldosterone system (RAAS) is over-activated, causing vasoconstriction, hypertension, elevated aldosterone levels and sympathetic tone, and eventually cardiac remodeling. Second, an endogenous compensatory mechanism, the natriuretic peptide (NP) system is also activated, albeit insufficiently to counteract the RAAS effects. Since NPs are degraded by the enzyme neprilysin, it was hypothesized that its inhibition could be an important therapeutic target in HF. Sacubitril/valsartan is the first of the class of dual neprilysin and angiotensin receptor inhibitors (ARNI). In patients with HFrEF, treatment with sacubitril/valsartan has demonstrated to significantly reduce mortality and the rates of hospitalization and rehospitalization for HF when compared to enalapril. This communication reviews in detail the demonstrated benefits of sacubitril/valsartan in the treatment of patients with HFrEF, including reduction of mortality and disease progression as well as improvement in cardiac remodeling and quality of life. The hemodynamic and organic effects arising from its dual mechanism of action, including the impact of neprilysin inhibition at the renal level, especially relevant in patients with type 2 diabetes mellitus, are also reviewed. Finally, the evidence on the demonstrated safety and tolerability profile of sacubitril/valsartan in the different subpopulations studied has been compiled. The review of this evidence, together with the recommendations of the latest clinical guidelines, position sacubitril/valsartan as a fundamental pillar in the treatment of patients with HFrEF.
format	article
author	Domingo Pascual-Figal Domingo Pascual-Figal Antoni Bayés-Genis Antoni Bayés-Genis Antoni Bayés-Genis Paola Beltrán-Troncoso Pedro Caravaca-Pérez Pedro Caravaca-Pérez Pedro Caravaca-Pérez Alicia Conde-Martel Maria G. Crespo-Leiro Maria G. Crespo-Leiro Juan F. Delgado Juan F. Delgado Juan F. Delgado Javier Díez Javier Díez Javier Díez Javier Díez Francesc Formiga Nicolás Manito
author_facet	Domingo Pascual-Figal Domingo Pascual-Figal Antoni Bayés-Genis Antoni Bayés-Genis Antoni Bayés-Genis Paola Beltrán-Troncoso Pedro Caravaca-Pérez Pedro Caravaca-Pérez Pedro Caravaca-Pérez Alicia Conde-Martel Maria G. Crespo-Leiro Maria G. Crespo-Leiro Juan F. Delgado Juan F. Delgado Juan F. Delgado Javier Díez Javier Díez Javier Díez Javier Díez Francesc Formiga Nicolás Manito
author_sort	Domingo Pascual-Figal
title	Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
title_short	Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
title_full	Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
title_fullStr	Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
title_full_unstemmed	Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review
title_sort	sacubitril-valsartan, clinical benefits and related mechanisms of action in heart failure with reduced ejection fraction. a review
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/367a0118f2f647ed9ac35f91293314da
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Sacubitril-Valsartan, Clinical Benefits and Related Mechanisms of Action in Heart Failure With Reduced Ejection Fraction. A Review

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