Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure: EMPEROR-Reduced.

Abstract

BACKGROUND:

Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.

OBJECTIVES:

This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).

METHODS:

Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.

RESULTS:

The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.

CONCLUSIONS:

In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).

• Authors: João Pedro Ferreira, Faiez Zannad, Stuart J Pocock, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Martina Brueckmann, Waheed Jamal, Dominik Steubl, Elke Schueler, Milton Packer
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 77 Issue 11 Pg. 1397-1407 (03 23 2021) ISSN: 1558-3597 [Electronic] United States
• PMID: 33736821 (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
• Mineralocorticoid Receptor Antagonists
• Sodium-Glucose Transporter 2 Inhibitors
• empagliflozin

Topics

• Aged
• Benzhydryl Compounds (administration & dosage, adverse effects)
• Drug Interactions
• Drug Monitoring (methods, statistics & numerical data)
• Drug Therapy, Combination (methods)
• Female
• Glucosides (administration & dosage, adverse effects)
• Heart Failure (drug therapy, mortality, physiopathology)
• Humans
• Hyperkalemia (chemically induced, diagnosis, prevention & control)
• Kidney Function Tests (methods)
• Male
• Mineralocorticoid Receptor Antagonists (administration & dosage, adverse effects)
• Outcome and Process Assessment, Health Care
• Sodium-Glucose Transporter 2 Inhibitors (administration & dosage, adverse effects)
• Stroke Volume (drug effects)
• Withholding Treatment (statistics & numerical data)