Author + information
- Received September 24, 2019
- Revision received June 25, 2020
- Accepted June 29, 2020
- Published online August 24, 2020.
- Andrew P. Ambrosy, MDa,b,∗ (, )@KPHeartDoc,
- Eugene Braunwald, MDc,
- David A. Morrow, MD, MPHc,
- Adam D. DeVore, MD, MHSd,e,
- Kevin McCague, MAf,
- Xiangyi Meng, MAf,
- Carol I. Duffy, DOf,
- Ricardo Rocha, MDf,
- Eric J. Velazquez, MDg,
- on behalf of the PIONEER-HF Investigators
- aDepartment of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, California
- bDivision of Research, Kaiser Permanente Northern California, Oakland, California
- cTIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts
- dDivision of Cardiology, Duke University Medical Center, Durham, North Carolina
- eDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- fNovartis Pharmaceuticals Corporation, East Hanover, New Jersey
- gSection of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut
- ↵∗Address for correspondence:
Dr. Andrew P. Ambrosy, Division of Research, Kaiser Permanente Northern California, 2000 Broadway Street, Oakland, California 94612.
Background The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction.
Objectives The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results.
Methods The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission.
Results At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro–B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups.
Conclusions Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro–B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890)
- acute decompensated heart failure
- angiotensin receptor neprilysin inhibitor
- de novo
- new onset
- reduced ejection fraction
- treatment naïve
The academic authors jointly with Novartis participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; review of the manuscript; and decision to submit the manuscript for publication. Dr. Ambrosy has received significant research funding from Amarin Pharma, Abbott Laboratories, Novartis, the National Heart, Lung, and Blood Institute, and the Kaiser Permanente Northern California Community Benefit Program; and has received modest reimbursement for travel from Novartis. Dr. Braunwald has research grant support through the Brigham and Women’s Hospital from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; and has served as a consultant for Amgen, Cardurion, MyoKardia, Novo Nordisk, and Verve. Dr. Morrow has received grants to Brigham and Women’s Hospital from Abbott Laboratories, AstraZeneca, BRAHMS, Daiichi-Sankyo, Eisai, GlaxoSmithKline, The Medicines Company, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Roche Diagnostics, Takeda, and Zora Biosciences; and has received consulting fees from Aralez, AstraZeneca, Bayer Pharma, InCarda, Novartis, and Roche Diagnostics. Dr. DeVore has received research funding from AstraZeneca, Amgen, the American Heart Association, Bayer, Luitpold Pharmaceuticals, Medtronic, the National Heart, Lung, and Blood Institute, Patient-Centered Outcomes Research Institute, and Novartis; and has served as a consultant with AstraZeneca, Bayer, LivaNova, Mardil Medical, Novartis, and Procyrion. Dr. Velazquez has received research funding from the National Heart, Lung, and Blood Institute and Novartis; and has received consulting fees from Novartis. Dr. Duffy, Mr. McCague, Mr. Meng, and Dr. Rocha are employees of Novartis Pharmaceuticals.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received September 24, 2019.
- Revision received June 25, 2020.
- Accepted June 29, 2020.
- 2020 American College of Cardiology Foundation
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