Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/16716
Title: Sacubitril/valsartan: beyond natriuretic peptides
Authors: Singh, Jagdeep SS
Burrell, Louise M
Cherif, Myriam
Squire, Iain B
Clark, Andrew L
Lang, Chim C
Date of Publication: 8-Jul-2017
Citation: Heart 2017; online first: 8 July
Abstract: Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation, resulting in the better outcomes observed.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16716
DOI: 10.1136/heartjnl-2017-311295
ORCID: 0000-0003-1863-7539
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/28689178
Type: Journal Article
Subject: Alzheimer’s disease
B-type natriuretic peptide
Sacubitril/valsartan
Angiotensin receptor-neprilysin inhibitor
Bradykinin
Mechanism of action
Natriuretic peptides
Appears in Collections:Journal articles

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