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Cited by 243Heart Failure Treatment and ManagementRenin-Angiotensin System StudiesCardiac Fibrosis and Remodeling

Effects of the Angiotensin‐Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta‐Analysis

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Wang, Yiwen, Zhou, Ran, Lu, Chi, Chen, Qing, Xu, Tongda, Li, Dongye·2019·Journal of the American Heart Association
DOI 10.1161/jaha.119.012272PMC PMC6662364
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Abstract

Background: The angiotensin‐receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin‐converting enzyme inhibitor enalapril in terms of reducing cardiovascular mortality in the PARADIGM‐HF (Prospective Comparison of ARNI with angiotensin‐converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study. However, the impact of ARNI on cardiac reverse remodeling (CRR) has not been established. Methods and Results: We conducted a meta‐analysis to compare the effects of ARNI versus angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers on CRR indices. We searched databases for studies published between 2010 and 2019 that reported CRR indices following ARNI administration. Effect size was expressed as mean difference (MD) with 95% CIs. Twenty studies enrolling 10 175 patients were included. ARNI improved functional capacity in patients with heart failure (HF) and a reduced ejection fraction (EF), including increasing New York Heart Association functional class (MD −0.79, 95% CI −0.86, −0.71) and 6‐minute walking distance (MD 27.62 m, 95% CI 15.76, 39.48). ARNI outperformed angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in terms of CRR indices, with striking changes in left ventricular EF, diameter, and volume. However, there were no significant improvements in indices except left ventricular mass index (MD −3.25 g/m 2 , 95% CI −3.78, −2.72) and left atrial volume (MD −7.20 mL, 95% CI −14.11, −0.29) in HF patients with preserved EF treated with ARNI. Improvements in CRR indices were observed at 3 months and became more significant with longer follow‐up to 12 months. The regression equation for the relationship between left ventricular EF and end‐diastolic dimension was y=0.041+0.071x+0.045x 2 +0.006x 3 . Conclusions: ARNI distinctly improved left ventricular size and hypertrophy compared with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in HF with reduced EF patients, even after short‐term follow‐up. Patients appeared to benefit more in terms of CRR treated with ARNI as early as possible and for at least 3 months. Further large sample trials are required to determine the effects of ARNI on CRR in HF with preserved EF patients.

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  • In a meta-analysis of 9 studies including 707 patients with HFrEF, LVEF increased by 4.9% (range, 4.13%-5.65%) after patients were switched to treatment with an ARNI.

    “In a meta-analysis of 9 studies including 707 patients with HFrEF, the LVEF increased by 4.9% (range, 4.13%-5.65%) after patients were switched to treatment with an ARNI.”

    From CCS/CHFS Heart Failure Guidelines Update: Defining a New Pharmacologic Standard of Care for Heart Failure With Reduced Ejection Fraction (2021) · cites this paper as [82]

    The Results (Effects of ARNI on CRR Indices; page unavailable) report a 4.89% increase in LVEF among HFrEF patients, with a 95% confidence interval of 4.13%–5.65%. The paper does not identify 707 patients for that estimate, and the Discussion says that more than 71% of patients in noncontrolled studies had transferred from ACEIs/ARBs to ARNI—not that all patients in the estimate had switched. The cited figures are confidence-interval bounds, not an observed range. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Wang, Y., Zhou, R., Lu, C., Chen, Q., Xu, T., & Li, D.
Affiliations
  • Xuzhou Medical College (CN)
  • Affiliated Hospital of Xuzhou Medical College (CN)
Corresponding author
  • Xu, Tongda
  • Li, Dongye
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-07-02
Volume
8
Issue
13
Pages
e012272-e012272
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.119.012272
PMC
PMC6662364
OpenAlex
W2954586029
Cited by
243
References
4
Citations by year
2026: 19 · 2025: 36 · 2024: 37 · 2023: 43 · 2022: 48 · 2021: 32 · 2020: 21 · 2019: 6
FWCI
4.84
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China
  • Xuzhou Medical University
  • National Science and Technology Planning Project
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
angiotensin receptor-neprilysin inhibitors, sacubitril/valsartan, reverse cardiac remodeling, heart failure, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, ACE inhibitors, angiotensin receptor blockers, left ventricular ejection fraction, left ventricular mass, left atrial volume, functional capacity
MeSH terms
Valsartan, Walk Test, Aminobutyrates, Biphenyl Compounds, Drug Combinations, Heart Failure, Humans, Stroke Volume, Tetrazoles, Treatment Outcome, Ventricular Remodeling, Angiotensin Receptor Antagonists, Atrial Remodeling

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