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

Jordan B King1, Adam P Bress1,2, Austin D Reese1

  • 1Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, Utah.

Pharmacotherapy
|September 26, 2015
PubMed

Insights

A new drug, LCZ696, combines valsartan and sacubitril to treat chronic heart failure with reduced ejection fraction (HFrEF). This novel pharmacotherapy increases natriuretic peptides, counterbalancing harmful neurohormones in HFrEF patients.

Area of Science:

  • Cardiology
  • Pharmacology
  • Biochemistry

Background:

  • A decade-long gap exists in new pharmacotherapy approvals for chronic heart failure with reduced ejection fraction (HFrEF).
  • Existing treatments for HFrEF have limitations in effectively managing neurohormonal imbalances.
  • Neprilysin inhibition presents a novel therapeutic target for HFrEF.

Purpose of the Study:

  • To provide a comprehensive overview of the new agent LCZ696 for HFrEF.
  • To discuss the pharmacology and pathophysiological role of LCZ696 in HFrEF.
  • To review clinical trial data and the therapeutic positioning of LCZ696.

Main Methods:

  • Review of existing literature on LCZ696, valsartan, and sacubitril.
  • Analysis of pharmacological mechanisms of neprilysin inhibition and natriuretic peptide elevation.
  • Synthesis of data from completed and ongoing clinical trials.

Main Results:

  • LCZ696, a combination of valsartan and sacubitril, enhances natriuretic peptide levels.
  • This mechanism counteracts the detrimental effects of neurohormonal activation in HFrEF.
  • Clinical trials indicate a significant role for LCZ696 in HFrEF management.

Conclusions:

  • LCZ696 represents a significant advancement in HFrEF pharmacotherapy.
  • Its unique mechanism offers a new approach to managing neurohormonal dysregulation.
  • Further clinical evaluation will define its optimal place in HFrEF treatment guidelines.

Keywords:
heart failure with reduced ejection fractionneprilysin inhibitionpharmacotherapysystolic heart failuretherapeutic review

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