Elsevier

JACC: Heart Failure

Volume 8, Issue 10, October 2020, Pages 834-843
JACC: Heart Failure

Focus Issue: Angiotensin-Neprilysin Inhibition: Novel Insights
Clinical Research
Efficacy and Safety of Sacubitril/Valsartan by Dose Level Achieved in the PIONEER-HF Trial

https://doi.org/10.1016/j.jchf.2020.06.008Get rights and content
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Abstract

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)

Key Words

heart failure
hospitalization
sacubitril/valsartan

Abbreviations and Acronyms

ADHF
acute decompensated heart failure
b.i.d.
twice a day
CI
confidence interval
GDMT
guideline-directed medical therapy
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
LVEF
left ventricular ejection fraction
NT-proBNP
N-terminal pro–B-type natriuretic peptide
SBP
systolic blood pressure

Cited by (0)

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.