Language

English

Publication Date

3-3-2026

Journal

ESC Heart Failure

DOI

10.1093/eschf/xvag095

PMID

41920861

PMCID

PMC13122610

PubMedCentral® Posted Date

3-31-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: Sacubitril/valsartan (Sac/Val) represents a cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. This systematic review provides a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sac/Val in patients with HFrEF.

Methods: A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines.

Results: The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac reverse remodeling and lower-grade mitral regurgitation. Despite these benefits, implementation gaps persist, with only 15%-25% of patients achieving target doses in clinical practice. The most common reported adverse event with Sac/Val was hypotension (up to 17.6%), though severe hyperkalaemia and renal decline were similar when compared with traditional renin angiotensin system inhibitors.

Conclusion: Real-world data mirror the efficacy and safety profiles seen in randomized controlled trials, establishing Sac/Val as a cornerstone of HFrEF therapy. However, significant barriers remain, including delayed initiation and suboptimal dose titration. Enhancing clinician and patient awareness is needed to bridge these implementation gaps and fully realize the drug's potential to reduce the global healthcare burden of HF.

Keywords

Humans, Heart Failure, Biphenyl Compounds, Aminobutyrates, Drug Combinations, Stroke Volume, Valsartan, Angiotensin Receptor Antagonists, Treatment Outcome, HFrEF, Sac/Val, Real world, Review

Published Open-Access

yes

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