Mineralocorticoid Receptor Antagonists and Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction.

BACKGROUND

Mineralocorticoid receptor antagonists (MRAs) may be beneficial in reducing heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. The effect of sodium-glucose cotransporter 2 inhibitors in patients with HF with preserved ejection fraction according to MRA background therapy has not been reported.

OBJECTIVES

The aim of this study was to examine the effect of empagliflozin in MRA users and nonusers in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial.

METHODS

Survival analyses were conducted comparing the effects of empagliflozin vs placebo in MRA users and nonusers at baseline with treatment-by-MRA use interaction terms.

RESULTS

A total of 5,988 patients were included, of whom 2,244 (37.5%) were using MRAs at baseline. MRA users had higher event rates than MRA nonusers (placebo group primary outcome 9.4 vs 8.2 events per 100 person-years). The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users (HR: 0.73 [95% CI: 0.62-0.87] and HR: 0.87 [95% CI: 0.71-1.06]; interaction P = 0.22). The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers than in MRA users (HR: 0.60 [95% CI: 0.47-0.77] and HR: 0.90 [95% CI: 0.68-1.19]; interaction P = 0.038). MRA users experienced almost twice as many hyperkalemia events as MRA nonusers, and empagliflozin reduced the risk for hyperkalemia or initiation of potassium binders regardless of MRA use (MRA nonusers: HR: 0.90 [95% CI: 0.69-1.19]; MRA users: HR: 0.74 [95% CI: 0.56-0.96]; interaction P = 0.29).

CONCLUSIONS

The benefit of empagliflozin to reduce the primary outcome was not significantly different between MRA nonusers and MRA users. The effect of empagliflozin to reduce first and recurrent HF hospitalizations was more pronounced in MRA nonusers. Empagliflozin reduced hyperkalemia, with no significant treatment-by-MRA subgroup interaction. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The EMPEROR-Reduced trial (NCT03057977) was funded by Boehringer Ingelheim and Eli Lilly. Dr Ferreira has received consulting fees from Boehringer Ingelheim during the conduct of the study. Dr Zannad has received personal fees from Boehringer Ingelheim during the conduct of the study; has received personal fees from Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer, and CellProthera outside the submitted work; and has received other support from CVCT and Cardiorenal, outside the submitted work. Dr Pocock received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Anker has received research support from Abbott Vascular and Vifor International; has received grants from Vifor; has received personal fees from Vifor, Bayer, Boehringer Ingelheim, Brahms, Novartis, Servier, Impulse Dynamics, Cardiac Dimensions, and Thermo Fisher Scientific; and has received grants and personal fees from Abbott Vascular, outside the submitted work. Dr Butler has received consultancy fees from Boehringer Ingelheim during the conduct of the study; and has received consultancy fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, BerlinCures, Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave, and Vifor, outside the submitted work. Dr Filippatos has received payment from Boehringer Ingelheim as a trial committee member during the conduct of the study; and has received payments from Medtronic, Vifor, Servier, and Novartis as a trial committee member, outside the submitted work. Dr Januzzi is supported by the Hutter Family Professorship; is a trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees and data and safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr Packer has received personal fees from Abbvie, Actavis, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Moderna, Novartis, Reata, Relypsa, and Salamandras. Dr Steubl and Ms Zeller are employees of Boehringer Ingelheim. Ms Schueler is an employee of mainanalytics, contracted by Boehringer Ingelheim.