title: The Role of Neprilysin Inhibitors in Cardiovascular Disease.
abstract: Heart failure affects over five million Americans each year and contributes to morbidity, mortality, and high health care costs. Despite the benefits of RAAS and SNS blockers, 5-year survival rates in patients with heart failure remain low, necessitating continued research and new drug targets. LCZ696 (sacubitril/valsartan) is an angiotensin-receptor neprilysin inhibitor recently approved for HFrEF, with dual actions that result in enhancement of natriuretic peptide levels and blockade of angiotensin II activities. This drug shows promise in further improving clinical outcomes in HFrEF and is being studied in patients with HFpEF. In the PARADIGM-HF study, LCZ696 (sacubitril/valsartan) was shown to reduce the composite of cardiovascular mortality and heart failure hospitalizations compared with enalapril in patients with HFrEF taking guideline-directed medical therapies and resulted in prolonged survival. In trials, hypotension occurred more frequently with LCZ696 (sacubitril/valsartan) compared to an ACE inhibitor, warranting careful dose titration. Further clinical experience with LCZ696 (sacubitril/valsartan) will provide additional information on tolerability in a broad range of patients of various demographics.
authors.affiliation: University of Wisconsin School of Pharmacy (J.M., O.V.), Madison, WI, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Mills
authors.affiliation: University of Wisconsin School of Pharmacy (J.M., O.V.), Madison, WI, USA. orly.vardeny@wisc.edu.|University of Wisconsin-Madison, Madison, WI, 53705-2222, USA. orly.vardeny@wisc.edu.
authors.forename: Orly
authors.initials: O
authors.lastname: Vardeny
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004338:Drug Combinations; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: Angiotension II; Cardiovascular mortality; HFpEF; HFrEF; Heart failure; Natriuretic peptide levels; Neprilysin inhibitor