Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial.

Abstract

BACKGROUND:

The relationship between the benefits of empagliflozin in heart failure with reduced ejection fraction (HFrEF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has not been reported.

OBJECTIVES:

The authors sought to evaluate the relationship between NT-proBNP and empagliflozin effects in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).

METHODS:

Patients with HFrEF were randomly assigned to placebo or empagliflozin 10 mg daily. NT-proBNP was measured at baseline, 4 weeks, 12 weeks, 52 weeks, and 100 weeks. Patients were divided into quartiles of baseline NT-proBNP.

RESULTS:

Incidence rates for each study outcome were 4- to 6-fold higher among those in the highest versus lowest NT-proBNP quartiles (≥3,480 vs <1,115 pg/mL). Study participants with higher NT-proBNP had 2- to 3-fold total hospitalizations higher than the lowest NT-proBNP quartile. Empagliflozin reduced risk for major cardiorenal events without heterogeneity across NT-proBNP quartiles (primary endpoint Pinteraction = 0.94; renal composite endpoint Pinteraction = 0.71). Empagliflozin treatment significantly reduced NT-proBNP at all timepoints examined; by 52 weeks, the adjusted mean difference from placebo was 13% (P < 0.001). An NT-proBNP in the lowest quartile (<1,115 pg/mL) 12 weeks after randomization was associated with lower risk for subsequent cardiovascular death or heart failure hospitalization regardless of baseline concentration. Treatment with empagliflozin resulted in 27% higher adjusted odds of an NT-proBNP concentration of <1,115 pg/mL by 12 weeks compared with placebo (P = 0.01).

CONCLUSIONS:

In EMPEROR-Reduced, higher baseline NT-proBNP concentrations were associated with greater risk for adverse heart failure or renal outcomes, but empagliflozin reduced risk regardless of baseline NT-proBNP concentration. The NT-proBNP concentration after treatment with empagliflozin better informs subsequent prognosis than pretreatment concentrations. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).

• Authors: James L Januzzi Jr, Faiez Zannad, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Stuart J Pocock, João Pedro Ferreira, Naveed Sattar, Subodh Verma, Ola Vedin, Janet Schnee, Tomoko Iwata, Dan Cotton, Milton Packer, EMPEROR-Reduced Trial Committees and Investigators
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 78 Issue 13 Pg. 1321-1332 (09 28 2021) ISSN: 1558-3597 [Electronic] United States
• PMID: 34556318 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Glucosides
• Peptide Fragments
• Sodium-Glucose Transporter 2 Inhibitors
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• empagliflozin

Topics

• Aged
• Benzhydryl Compounds (pharmacology, therapeutic use)
• Female
• Glucosides (pharmacology, therapeutic use)
• Heart Failure, Systolic (blood, drug therapy)
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Sodium-Glucose Transporter 2 Inhibitors (pharmacology, therapeutic use)