Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review

Pharmacotherapy. 2015 Sep;35(9):823-37. doi: 10.1002/phar.1629.

Abstract

There has been a 10-year hiatus in the approval of a new pharmacotherapy for patients with chronic heart failure with a reduced ejection fraction (HFrEF). Combining an angiotensin receptor blocker, valsartan, with sacubitril, an inhibitor of neprilysin, results in increasing levels of natriuretic peptides that counterbalance high circulating levels of neurohormones in HFrEF. This has resulted in the development of a new agent, LCZ696. A comprehensive overview of LCZ696, its pharmacology, its role in the pathophysiology of HFrEF, completed and future clinical trial information, specific critical issues, and the place of LCZ696 in HFrEF therapy are presented.

Keywords: heart failure with reduced ejection fraction; neprilysin inhibition; pharmacotherapy; systolic heart failure; therapeutic review.

Publication types

  • Review

MeSH terms

  • Aminobutyrates / pharmacology
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds
  • Chronic Disease
  • Drug Combinations
  • Drug Design
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Neprilysin / antagonists & inhibitors*
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Tetrazoles
  • Valsartan
  • Neprilysin
  • sacubitril and valsartan sodium hydrate drug combination