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Review
. 2025 Jul 17:11:e16.
doi: 10.15420/cfr.2024.39. eCollection 2025.

Improving the Management of Patients with Heart Failure with Reduced Ejection Fraction in Clinical Practice: The Case for Angiotensin Receptor-Neprilysin Inhibitor

Affiliations
Review

Improving the Management of Patients with Heart Failure with Reduced Ejection Fraction in Clinical Practice: The Case for Angiotensin Receptor-Neprilysin Inhibitor

Massimo Iacoviello et al. Card Fail Rev. .

Abstract

The high risk of adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF) demands urgent efforts in the initiation of guideline-directed medical therapy to reduce morbidity and mortality. Angiotensin receptor-neprilysin inhibitor showed substantial benefits in reducing the risks of heart failure hospitalisation and cardiovascular mortality in HFrEF patients. Therefore, the European Society of Cardiology 2021 guidelines recommend angiotensin receptor-neprilysin inhibitor as a first-line therapy for HFrEF patients. The guidelines emphasise the importance of the early use and rapid titration of the 'four pillars' in HFrEF: angiotensin receptor-neprilysin inhibitor, β-blockers, sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists. However, real-world application of the guidelines remains suboptimal, limiting patient outcomes. This statement paper investigates the barriers to the use of the 'four pillars', and aims to give guidance to improve their implementation in different HFrEF patient types.

Keywords: Heart failure with reduced ejection fraction; angiotensin receptor–neprilysin inhibitor; clinical inertia; mineralocorticoid receptor antagonists; sodium-glucose cotransporter 2 inhibitors; β-blockers.

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Conflict of interest statement

Disclosures: MD is a consultant for Bayer. All other authors have no conflicts of interest to declare.

References

    1. Shahim B, Kapelios CJ, Savarese G, Lund LH. Global public health burden of heart failure: an updated review. Card Fail Rev. 2023;9:e11. doi: 10.15420/cfr.2023.05. - DOI - PMC - PubMed
    1. McDonagh TA, Metra M, Adamo M et al. Focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2023;44:3627–39. doi: 10.1093/eurheartj/ehad195. - DOI - PubMed
    1. Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart failure with reduced ejection fraction: a review. JAMA. 2020;324:488–504. doi: 10.1001/jama.2020.10262. - DOI - PubMed
    1. McMurray JJV, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. doi: 10.1056/NEJMoa1409077. - DOI - PubMed
    1. Velazquez EJ, Morrow DA, DeVore AD et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48. doi: 10.1056/NEJMoa1812851. - DOI - PubMed

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