Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure.

Abstract

BACKGROUND:

The efficacy and safety of sacubitril/valsartan in patients hospitalized with heart failure (HF) across the spectrum of left ventricular ejection fraction (EF) has not been described.

OBJECTIVES:

Data from randomized trials of sacubitril/valsartan in HF patients with EF ≤40% (PIONEER-HF [Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode] trial) and >40% (PARAGLIDE-HF [Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF] trial) following recent worsening heart failure (WHF) were pooled to examine treatment effect across the EF spectrum.

METHODS:

The PIONEER-HF and PARAGLIDE-HF trials were double-blind, randomized trials of sacubitril/valsartan vs control therapy (enalapril or valsartan, respectively). All participants in the PIONEER-HF trial and 69.5% in the PARAGLIDE-HF trial were enrolled during hospitalization for HF after stabilization. The remainder in the PARAGLIDE-HF trial were enrolled ≤30 days after a WHF event. The primary endpoint of both trials was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8. Adjudicated clinical endpoints were analyzed through the end of follow-up, adjusting for trial.

RESULTS:

The pooled analysis included 1,347 patients (881 from PIONEER-HF, 466 from PARAGLIDE-HF). Baseline characteristics included median age 66 years, 36% women, 31% Black, 34% de novo HF, and median EF 30%. The reduction in NT-proBNP was 24% greater with sacubitril/valsartan vs control therapy (n = 1,130; ratio of change = 0.76; 95% CI: 0.69-0.83; P < 0.0001). Cardiovascular death or hospitalization for HF was reduced by 30% with sacubitril/valsartan vs control therapy (HR: 0.70; 95% CI: 0.54-0.91; P = 0.0077). This effect was consistent across the spectrum of EF ≤60%. Sacubitril/valsartan increased symptomatic hypotension (risk ratio: 1.35; 95% CI: 1.05-1.72).

CONCLUSIONS:

In patients stabilized after WHF, sacubitril/valsartan led to a greater reduction in plasma NT-proBNP and improved clinical outcome compared with control therapy, in particular across the spectrum of EF ≤60%. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890; Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event [HFpEF Decompensation] Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation [PARAGLIDE-HF]; NCT03988634).

• Authors: David A Morrow, Eric J Velazquez, Akshay S Desai, Adam D DeVore, Serge Lepage, Jeong-Gun Park, Kavita Sharma, Scott D Solomon, Randall C Starling, Jonathan H Ward, Kristin M Williamson, Shelley Zieroth, Adrian F Hernandez, Robert J Mentz, Eugene Braunwald
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 83 Issue 12 Pg. 1123-1132 (Mar 26 2024) ISSN: 1558-3597 [Electronic] United States
• PMID: 38508844 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Biphenyl Compounds
• Drug Combinations
• Enalapril
• sacubitril
• Tetrazoles
• Valsartan

Topics

• Aged
• Female
• Humans
• Male
• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use, pharmacology)
• Biphenyl Compounds (therapeutic use)
• Drug Combinations
• Enalapril (therapeutic use)
• Heart Failure
• Stroke Volume
• Tetrazoles
• Valsartan (therapeutic use)
• Ventricular Function, Left
• Double-Blind Method