LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure

Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):14-22. doi: 10.1111/bcpt.12453. Epub 2015 Sep 4.

Abstract

The aim of this MiniReview was to introduce the newly invented dual-acting drug valsartan/sacubitril (LCZ696), which combines an angiotensin receptor blocker (valsartan) with sacubitril, a specific inhibitor of the neutral endopeptidase (NEP) that degrades vasoactive peptides, including natriuretic peptides ANP and BNP, but also glucagon, enkephalins and bradykinin, among others. The MiniReview presents the data of four available trials NCT01193101, NCT00549770, NCT00887588 and NCT01035255 and provides the current knowledge about LCZ696 effects in patients with hypertension and heart failure. Presently, patients suffering from hypertension and heart failure are treated with ACE inhibitors or angiotensin receptor antagonists often in combination with other drugs. These current medications lead to a reduction in blood pressure in hypertensive patients and a decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, but not in patients with heart failure with preserved ejection fraction. LCZ696 had been tested to utilize the beneficial properties of natriuretic peptides in combination with angiotensin receptor antagonism. It induces even greater blood pressure reductions and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, while patients with heart failure with preserved ejection fraction show lowered blood pressure and decreased NT-pro-BNP levels. Although long-term studies remain to be performed, these initial data suggest that there is a potential clinical benefit of LCZ696 in the treatment of hypertension and heart failure.

Publication types

  • Review

MeSH terms

  • Aminobutyrates / administration & dosage
  • Aminobutyrates / adverse effects
  • Aminobutyrates / pharmacokinetics
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / pharmacokinetics
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Animals
  • Biphenyl Compounds
  • Drug Combinations
  • Heart Failure / drug therapy*
  • Heart Failure / enzymology
  • Heart Failure / metabolism
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / enzymology
  • Hypertension / metabolism
  • Molecular Structure
  • Natriuretic Peptides / metabolism
  • Neprilysin / antagonists & inhibitors
  • Randomized Controlled Trials as Topic
  • Renin-Angiotensin System / drug effects
  • Tetrazoles / administration & dosage
  • Tetrazoles / adverse effects
  • Tetrazoles / pharmacokinetics
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Valsartan

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00549770
  • ClinicalTrials.gov/NCT00887588
  • ClinicalTrials.gov/NCT01035255
  • ClinicalTrials.gov/NCT01193101