Author + information
- Received March 5, 2020
- Revision received June 2, 2020
- Accepted June 2, 2020
- Published online September 28, 2020.
- David D. Berg, MD, MPHa,∗ (, )
- Eugene Braunwald, MDa,
- Adam D. DeVore, MD, MHSb,
- Anuradha Lala, MDc,
- Sean P. Pinney, MDc,
- Carol I. Duffy, DOd,
- Yared Gurmu, PhDa,
- Eric J. Velazquez, MDe and
- David A. Morrow, MD, MPHa
- aTIMI Study Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- bDuke Clinical Research Institute, Duke University, Durham, North Carolina
- cZena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- dNovartis Pharmaceuticals Corporation, East Hanover, New Jersey
- eDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- ↵∗Address for correspondence:
Dr. David D. Berg, TIMI Study Group, 60 Fenwood Road, Suite 7022, Boston, Massachusetts 02115.
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 (pinteraction = 0.69), the reduction in cardiovascular death or rehospitalization for heart failure (pinteraction = 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)
The PIONEER-HF trial was funded by Novartis Pharmaceutical Corp. For the work under consideration, Dr. Braunwald reports grant support to his institution from Novartis for the conduct of the PIONEER-HF Trial, for his serving on the Executive Committee of the PARADISE trial, the Steering Committee of the PARAGLIDE trial, and for his participation in an Advisory Board meeting; outside the submitted work; reports grants to his institution from AstraZeneca, Daiichi Sankyo, and Merck; and has received personal fees for consultancies with Amgen, Cardurion, MyoKardia, NovoNordisk, and Verve Dr. DeVore has received research funding from AstraZeneca, Amgen, the American Heart Association, Bayer, Luitpold Pharmaceuticals, Medtronic, the National Heart, Lung, and Blood Institute (NHLBI), PCORI, and Novartis; and has served as a consultant for AstraZeneca, LivaNova, Mardil Medical, Novartis, and Procyrion. Dr. Pinney has received consulting fees from Abbott, CareDx, and Medtronic. Dr. Duffy is an employee of Novartis Pharmaceuticals Corp. Dr. Gurmu has received grant support from Novartis. Dr. Velazquez has received grants from Novartis, Amgen, Phillips, and NHLBI/National Institutes of Health. Dr. Morrow has received grants from Abbott Laboratories, Amgen, AstraZeneca, Eisai, GlaxoSmithKline, Medicines Company, Merck, Novartis, Pfizer, Roche Diagnostics, and Takeda; and has received personal fees from Abbott Laboratories, Aralez, AstraZeneca, Bayer Pharma, GlaxoSmithKline, InCarda, Merck, Peloton, and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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: Heart Failure author instructions page.
- Received March 5, 2020.
- Revision received June 2, 2020.
- Accepted June 2, 2020.
- 2020 American College of Cardiology Foundation
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