Efficacy and safety of sacubitril/valsartan by dose level achieved in the PIONEER-HF trial
Open accessAbstract
Objectives This study sought to evaluate the efficacy and safety of sacubitril/valsartan according to dose level achieved in the PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode) trial.Background In patients hospitalized for acute decompensated heart failure (ADHF), in-hospital initiation and continuation of sacubitril/valsartan as compared with enalapril is well tolerated, achieves a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and reduces the risk of cardiovascular death or rehospitalization for HF through 8 weeks. However, not all patients achieve the target dose of sacubitril/valsartan, and its efficacy and safety in such patients are of interest.Methods PIONEER-HF was a randomized, double-blind, active-controlled trial of sacubitril/valsartan versus enalapril in 881 patients stabilized during hospitalization for ADHF. Blinded study medication was administered for 8 weeks, with initial dosing selected based on the systolic blood pressure at randomization and titrated toward a target of sacubitril/valsartan 97/103 mg twice daily, or enalapril 10 mg twice daily, with an algorithm based on systolic blood pressure and the investigator's assessment of tolerability.Results At 4 weeks, 199 (55%) patients allocated to sacubitril/valsartan and 211 (60%) patients allocated to enalapril were dispensed the target dose. Baseline characteristics were similar in the 2 treatment groups within each dose level. There was no heterogeneity across dose levels in the effect of sacubitril/valsartan on the reduction in NT-proBNP (p interaction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (p interaction = 0.42), or the pre-specified adverse events of special interest through 8 weeks.Conclusions In hemodynamically stabilized patients with ADHF, the efficacy and safety of sacubitril/valsartan are generally consistent across dose levels. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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A recent analysis of the PIONEER-HF trial showed that the efficacy and safety of sacubitril-valsartan are generally similar across various dose levels.
“A recent additional analysis has shown that the efficacy and safety of sacubitril-valsartan is generally similar across various dose levels,10”
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 [10]
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- Authors
- Berg, D. D., Braunwald, E., DeVore, A. D., Lala, A., Pinney, S. P., Duffy, C. I., Gurmu, Y., Velazquez, E. J., & Morrow, D. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Duke University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Novartis (United States) (US)
- Yale University (US)
- Corresponding author
- Berg, David D.
- ORCID
- Venue
- JACC: Heart Failure
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 8
- Issue
- 10
- Pages
- 834-843
- ISSN
- 2213-1779 (ISSN-L)
- PMC
- PMC7541586
- OpenAlex
- W3048688534
- Cited by
- 36
- References
- 13
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 4 · 2021: 5
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Amgen
- Luitpold Pharmaceuticals
- Patient-Centered Outcomes Research Institute
- AstraZeneca
- MyoKardia
- Takeda Pharmaceuticals U.S.A.
- GlaxoSmithKline
- Daiichi-Sankyo
- Novartis Pharmaceuticals Corporation
- Merck
- Eisai
- Bayer Fund
- Abbott Laboratories
- Novo Nordisk
- CareDx
- Medtronic
- National Heart, Lung, and Blood Institute
- American Heart Association
- Novartis
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- sacubitril/valsartan, dose titration, acute decompensated heart failure, enalapril, NT-proBNP, drug efficacy, drug safety, adverse events, heart failure pharmacotherapy
- MeSH terms
- Valsartan, Aminobutyrates, Angiotensin-Converting Enzyme Inhibitors, Biphenyl Compounds, Drug Combinations, Female, Heart Failure, Humans, Stroke Volume, Ventricular Function, Left, Angiotensin Receptor Antagonists
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