Neprilysin Inhibitors: Emerging Therapy for Heart Failure

Annu Rev Med. 2017 Jan 14:68:41-49. doi: 10.1146/annurev-med-052915-015509. Epub 2016 Sep 21.

Abstract

Biologically active natriuretic peptides (NPs) are an integral part of cardiac homeostasis as they help to maintain sodium and fluid balance. When homeostasis is perturbed by neurohormonal activation in heart failure, levels of NPs rise in response. Neprilysin (NEP) is a naturally occuring enzyme that breaks down NPs. Scientists have recently discovered a novel pharmacologic agent that combines a NEP inhibitor and an angiotensin receptor blocker. In a large clinical trial, this new drug was found to reduce hospitalization and mortality in systolic heart failure. The challenges of implementing this therapy include patient selection, cost, and risk of side effects including angioedema and Alzheimer's disease.

Keywords: LCZ696; angiotensin receptor antagonist and neprilysin inhibitor (ARNI); angiotensin receptor antagonists; angiotensin-converting enzyme (ACE) inhibitors; heart failure; sacubitril; valsartan.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / chemically induced
  • Aminobutyrates / adverse effects
  • Aminobutyrates / economics
  • Aminobutyrates / therapeutic use*
  • Angioedema / chemically induced
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Biphenyl Compounds
  • Drug Combinations
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Neprilysin / antagonists & inhibitors*
  • Neprilysin / metabolism
  • Patient Selection
  • Pyridines / adverse effects
  • Stroke Volume
  • Tetrazoles / adverse effects
  • Tetrazoles / economics
  • Tetrazoles / therapeutic use*
  • Thiazepines / adverse effects
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biphenyl Compounds
  • Drug Combinations
  • Pyridines
  • Tetrazoles
  • Thiazepines
  • omapatrilat
  • Valsartan
  • Neprilysin
  • sacubitril and valsartan sodium hydrate drug combination