title: Angiotensin receptor neprilysin inhibitor LCZ696: pharmacology, pharmacokinetics and clinical development.
abstract: Heart failure still has a significant disease burden with poor outcomes worldwide despite advances in therapy. The standard therapies have been focused on blockade of renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid antagonists and the sympathetic nervous system with β-blockers. The natriuretic peptide system is a potential counter-regulatory system that promotes vasodilatation and natriuresis. Angiotensin receptor neprilysin inhibitors are a new class drug capable of blocking the renin-angiotensin-aldosterone system and enhancing the natriuretic peptide system to improve neurohormonal balance. The success of the PARADIGM-HF trial with LCZ696 and its approval for heart failure treatment is likely to generate a paradigm shift. This review summarises the current knowledge of LCZ696 with a focus on pharmacology, pharmacokinetics and pharmacodynamics, mechanisms of action, clinical efficacy and safety.
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.|School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, Australia.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.|NHMRC Cardiovascular Centre of Research Excellence, School of Public Health, Curtin University, Perth, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Reid
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Bing H
authors.initials: BH
authors.lastname: Wang
mesh_terms: D000613:Aminobutyrates / Q000493:pharmacokinetics / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D011945:Receptors, Angiotensin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: angiotensin receptor neprilysin inhibitor; heart failure; neprilysin inhibitor