Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data

Joseph J Cuthbert,1 Pierpaolo Pellicori,2 Andrew L Clark1 1Department of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Kingston upon Hull HU16 5JQ, UK; 2Robertson Institute of Biostatistics and Clinical Trials Unit,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cuthbert JJ, Pellicori P, Clark AL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	sacubitril valsartan heart failure paradigm-hf paragon-hf natriuretic peptide angiotensin receptor neprilysin inhibitor Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/f8ba4bb6b9594b65945321b7181eeeb2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f8ba4bb6b9594b65945321b7181eeeb2
record_format	dspace
spelling	oai:doaj.org-article:f8ba4bb6b9594b65945321b7181eeeb22021-12-02T12:29:41ZCardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data1178-203Xhttps://doaj.org/article/f8ba4bb6b9594b65945321b7181eeeb22020-08-01T00:00:00Zhttps://www.dovepress.com/cardiovascular-outcomes-with-sacubitril-valsartan-in-heart-failure-eme-peer-reviewed-article-TCRMhttps://doaj.org/toc/1178-203XJoseph J Cuthbert,1 Pierpaolo Pellicori,2 Andrew L Clark1 1Department of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Kingston upon Hull HU16 5JQ, UK; 2Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, University Avenue, Glasgow G12 8QQ, UKCorrespondence: Joseph J CuthbertDepartment of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Cottingham, Kingston upon Hull HU16 5JQ, UKTel + 44 (0)1482 461776Fax + 44 (0)1482 461779Email joe.cuthbert@hey.nhs.ukAbstract: One of the defining features of heart failure (HF) is neurohormonal activation. The renin-angiotensin-aldosterone-system (RAAS) and sympathetic nervous system (SNS) cause vasoconstriction and fluid retention and, in response, the secretion of natriuretic peptides (NPs) from volume and pressure-overloaded myocardium promotes vasodilation and diuresis. Inhibition of the RAAS with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been the cornerstone of medical treatment for HF with a reduced ejection fraction (HFrEF) but, until recently, it was unclear how the beneficial effects of NPs may be augmented in patients with HF. Neprilysin, a metalloproteinase widely distributed throughout the body, plays a role in degrading the gross excess of circulating NPs in patients with HF. Early studies of neprilysin inhibition suggested possible physiological benefits. In 2014, the PARADIGM-HF trial found that sacubitril-valsartan, a combination of the ARB valsartan, and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with HFrEF, reducing the relative risk of cardiovascular (CV) death or first hospitalisation with HF by 20%. Almost half of the patients with HF symptoms have a “preserved” ejection fraction (HFpEF); however, the PARAGON-HF study found that sacubitril-valsartan in patients with LVEF ≥ 45% had no effect on CV death or first and recurrent hospitalisations with HF compared to valsartan. Guidelines across the world have changed to include sacubitril-valsartan for patients with HFrEF yet, nearly 6 years after PARADIGM-HF, there is still uncertainty as to when and in whom sacubitril-valsartan should be started. Furthermore, there may yet be subsets of patients with HFpEF who might benefit from treatment with sacubitril-valsartan. This review will describe the mechanisms behind the outcome benefit of sacubitril-valsartan in patients with HFrEF and to consider its future role in the management of patients with HF.Keywords: sacubitril-valsartan, heart failure, PARADIGM-HF, PARAGON-HF, natriuretic peptide, angiotensin receptor neprilysin inhibitorCuthbert JJPellicori PClark ALDove Medical Pressarticlesacubitril valsartanheart failureparadigm-hfparagon-hfnatriuretic peptideangiotensin receptor neprilysin inhibitorTherapeutics. PharmacologyRM1-950ENTherapeutics and Clinical Risk Management, Vol Volume 16, Pp 715-726 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	sacubitril valsartan heart failure paradigm-hf paragon-hf natriuretic peptide angiotensin receptor neprilysin inhibitor Therapeutics. Pharmacology RM1-950
spellingShingle	sacubitril valsartan heart failure paradigm-hf paragon-hf natriuretic peptide angiotensin receptor neprilysin inhibitor Therapeutics. Pharmacology RM1-950 Cuthbert JJ Pellicori P Clark AL Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
description	Joseph J Cuthbert,1 Pierpaolo Pellicori,2 Andrew L Clark1 1Department of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Kingston upon Hull HU16 5JQ, UK; 2Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, University Avenue, Glasgow G12 8QQ, UKCorrespondence: Joseph J CuthbertDepartment of Academic Cardiology, Hull York Medical School, Hull and East Yorkshire Medical Research and Teaching Centre, Castle Hill Hospital, Cottingham, Kingston upon Hull HU16 5JQ, UKTel + 44 (0)1482 461776Fax + 44 (0)1482 461779Email joe.cuthbert@hey.nhs.ukAbstract: One of the defining features of heart failure (HF) is neurohormonal activation. The renin-angiotensin-aldosterone-system (RAAS) and sympathetic nervous system (SNS) cause vasoconstriction and fluid retention and, in response, the secretion of natriuretic peptides (NPs) from volume and pressure-overloaded myocardium promotes vasodilation and diuresis. Inhibition of the RAAS with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been the cornerstone of medical treatment for HF with a reduced ejection fraction (HFrEF) but, until recently, it was unclear how the beneficial effects of NPs may be augmented in patients with HF. Neprilysin, a metalloproteinase widely distributed throughout the body, plays a role in degrading the gross excess of circulating NPs in patients with HF. Early studies of neprilysin inhibition suggested possible physiological benefits. In 2014, the PARADIGM-HF trial found that sacubitril-valsartan, a combination of the ARB valsartan, and the neprilysin inhibitor sacubitril, was superior to enalapril in patients with HFrEF, reducing the relative risk of cardiovascular (CV) death or first hospitalisation with HF by 20%. Almost half of the patients with HF symptoms have a “preserved” ejection fraction (HFpEF); however, the PARAGON-HF study found that sacubitril-valsartan in patients with LVEF ≥ 45% had no effect on CV death or first and recurrent hospitalisations with HF compared to valsartan. Guidelines across the world have changed to include sacubitril-valsartan for patients with HFrEF yet, nearly 6 years after PARADIGM-HF, there is still uncertainty as to when and in whom sacubitril-valsartan should be started. Furthermore, there may yet be subsets of patients with HFpEF who might benefit from treatment with sacubitril-valsartan. This review will describe the mechanisms behind the outcome benefit of sacubitril-valsartan in patients with HFrEF and to consider its future role in the management of patients with HF.Keywords: sacubitril-valsartan, heart failure, PARADIGM-HF, PARAGON-HF, natriuretic peptide, angiotensin receptor neprilysin inhibitor
format	article
author	Cuthbert JJ Pellicori P Clark AL
author_facet	Cuthbert JJ Pellicori P Clark AL
author_sort	Cuthbert JJ
title	Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
title_short	Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
title_full	Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
title_fullStr	Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
title_full_unstemmed	Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data
title_sort	cardiovascular outcomes with sacubitril-valsartan in heart failure: emerging clinical data
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/f8ba4bb6b9594b65945321b7181eeeb2
work_keys_str_mv	AT cuthbertjj cardiovascularoutcomeswithsacubitrilvalsartaninheartfailureemergingclinicaldata AT pellicorip cardiovascularoutcomeswithsacubitrilvalsartaninheartfailureemergingclinicaldata AT clarkal cardiovascularoutcomeswithsacubitrilvalsartaninheartfailureemergingclinicaldata
_version_	1718394491586478080

Cardiovascular Outcomes with Sacubitril-Valsartan in Heart Failure: Emerging Clinical Data

Ejemplares similares