Role of Angiotensin Receptor-Neprilysin Inhibition in Heart Failure

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Updated: Mar 19, 2026

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

4.4K

Stuart B Prenner1, Sanjiv J Shah1, Clyde W Yancy2

  • 1Division of Cardiology, Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, 676 N St. Clair, Suite 600, Chicago, IL, 60611, USA.

Current Atherosclerosis Reports
|June 22, 2016
PubMed

Insights

The combination of valsartan and sacubitril (LCZ696) significantly reduces cardiovascular mortality in heart failure with reduced ejection fraction (HFrEF) patients compared to ACE inhibitors. This novel therapy offers substantial benefits, though careful patient selection is needed due to potential hypotension.

Area of Science:

  • Cardiology
  • Pharmacology
  • Heart Failure Research

Background:

  • Heart failure with reduced ejection fraction (HFrEF) management has advanced with numerous therapies.
  • The introduction of valsartan and sacubitril (LCZ696) in 2015 marked a significant shift in HFrEF treatment.
  • LCZ696 is a novel drug inhibiting both the renin-angiotensin system and potentiating the natriuretic peptide system.

Purpose of the Study:

  • To evaluate the efficacy and safety of LCZ696 compared to traditional therapies for HFrEF.
  • To assess the impact of LCZ696 on cardiovascular mortality and morbidity.
  • To explore the novel mechanistic approach of LCZ696 in heart failure management.

Main Methods:

  • The Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial was a key study.
  • Comparison of LCZ696 against an angiotensin-converting enzyme (ACE) inhibitor was performed.
  • Patient outcomes including cardiovascular mortality, total mortality, and morbidity were assessed.

Main Results:

  • LCZ696 demonstrated a 20% reduction in cardiovascular mortality (NNT 32) and total mortality (NNT 36) compared to ACE inhibitors.
  • Morbidity benefits were observed as early as 1 month after initiating LCZ696.
  • Hypotension affected 20% of patients during the run-in phase, and angioedema was a safety concern.

Conclusions:

  • LCZ696 represents a significant advancement in HFrEF treatment, offering superior outcomes to ACE inhibitors.
  • The drug's novel dual mechanism provides substantial cardiovascular benefits.
  • Further research is ongoing to evaluate LCZ696 in other cardiovascular populations, including heart failure with preserved ejection fraction.
Abstract

Keywords:
Clinical trialHeart failureNatriuretic peptidesNeprilysin inhibition

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