title: Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond.
abstract: Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction.
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Jagdeep S S
authors.initials: JS
authors.lastname: Singh
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Chim C
authors.initials: CC
authors.lastname: Lang
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007189:Indans / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D015260:Neprilysin / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D013318:Stroke Volume; D013777:Tetrazoles / Q000494:pharmacology*; D013841:Thiazepines / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004338:Drug Combinations; D007189:Indans; D011422:Propionates; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D013841:Thiazepines; D020097:Natriuretic Peptide, Brain; C106266:omapatrilat; D000068756:Valsartan; C062766:candoxatril; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: angiotensin receptor-neprilysin inhibitor; candoxatril; heart failure; heart failure with preserved ejection fraction; hypertension; myocardial infarction; nesiritide; omapatrilat; renal impairment