title: Neprilysin inhibition to treat heart failure: a tale of science, serendipity, and second chances.
abstract: This review describes the role of neprilysin (also known as neutral endopeptidase or enkephalinase) in the degradation of natriuretic and other vasoactive peptides, including bradykinin and adrenomedullin. The initial development of neprilysin inhibitors, then angiotensin converting enzyme-neprilysin inhibitors and, most recently, the angiotensin receptor neprilysin inhibitor (ARNI) LCZ696 (sacubitril valsartan) as an extension of the nurohumoral basis for the treatment of heart failure is also summarised. Finally, the implications of the compelling benefits of LCZ696 compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) is discussed.
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000613:Aminobutyrates / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004338:Drug Combinations; D004656:Enalapril / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Adrenomedullin; Angiotensin; Angiotensin converting enzyme; Bradykinin; Ejection fraction; Enkephalinase; Heart failure; Natriuretic peptides; Neprilysin; Neuroendocrine; Neurohormonal; Neurohumoral; Neutral endopeptidase 24.11