Angiotensin receptor neprilysin inhibitor LCZ696: pharmacology, pharmacokinetics and clinical development

Future Cardiol. 2017 Mar;13(2):103-115. doi: 10.2217/fca-2016-0057. Epub 2016 Nov 28.

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.

Keywords: angiotensin receptor neprilysin inhibitor; heart failure; neprilysin inhibitor.

MeSH terms

  • Aminobutyrates / pharmacokinetics
  • Aminobutyrates / pharmacology*
  • Angiotensin Receptor Antagonists / pharmacokinetics
  • Angiotensin Receptor Antagonists / pharmacology*
  • Biphenyl Compounds
  • Drug Combinations
  • Heart Failure / drug therapy*
  • Humans
  • Neprilysin / antagonists & inhibitors*
  • Receptors, Angiotensin / drug effects
  • Renin-Angiotensin System / drug effects
  • Tetrazoles / pharmacokinetics
  • Tetrazoles / pharmacology*
  • Valsartan

Substances

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