Heart Failure Outcomes and Empagliflozin Effects in Patients with Heart Failure and Reduced Ejection Fraction in Sinus Rhythm or Atrial Fibrillation: Data from EMPEROR-Reduced
Year: 2025
Type: article
Abstract: AIMS: Empagliflozin reduces cardiovascular death (CVD) or hospitalization for heart failure (HHF), slows estimated glomerular filtration rate (eGFR) decline and improves quality of life (QoL) in heart failure with reduced ejection fraction (HFrEF). Whether the effect of empagliflozin is consistent according to atrial fibrillation (AF) status is worth exploring. METHODS AND RESULTS: The impact of AF versus sinus rhythm (SR) on outcomes as well as on eGFR decline and QoL were studied post-hoc in EMPEROR-Reduced. Of patients with available rhythm analyses and after exclusion of patients with missing or paced rhythms, 2785 were included (AF, n = 928, SR, n = 1857). Differences were not significant for the primary endpoint (p = 0.66), first (p = 0.19) and recurrent HHF (p = 0.45). On placebo, alcohol consumption (interaction p = 0.32), body mass index (interaction p = 0.93), diabetes (interaction p = 0.52), hypertension (interaction p = 0.24) were not different between AF and SR. Low ejection fraction and high Kidney Disease: Improving Global Outcomes (KDIGO) class had higher event rates but without interaction between SR and AF, respectively. After a median follow-up of 20 months, empagliflozin reduced CVD or HHF compared to placebo in AF and SR (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.63-1.08; and HR 0.69, 95% CI 0.56-0.84; interaction p = 0.29). The same applied to time to first HHF (interaction p = 0.20), while there was a borderline but insignificant interaction for first and recurrent HHF (p = 0.10). The effect on annual eGFR decline and QoL scores was not different. Incident AF was numerically lower but formally not significantly different (HR 0.66, 95% CI 0.40-1.09, p = 0.11, empagliflozin vs. placebo). CONCLUSIONS: In HFrEF, AF did not significantly modify outcomes after adjustment and did not associate with eGFR slopes. Empagliflozin reduced outcomes, eGFR decline and improved QoL regardless of AF or SR and probably reduced incident AF.
DOI: 10.1002/ejhf.70021
Institutions: Universitätsklinikum des Saarlandes, Saarland University, University of Mississippi Medical Center, University of Mississippi, Baylor Scott & White Research Institute, National and Kapodistrian University of Athens, University General Hospital Attikon, Inserm, Universidade do Porto, Centre Hospitalier Régional et Universitaire de Nancy, Centre d'Investigation Clinique Pierre Drouin, Défaillance Cardiovasculaire Aiguë et Chronique, Université de Lorraine, London School of Hygiene & Tropical Medicine, Boehringer Ingelheim (Germany), Heidelberg University, Medizinische Fakultät Mannheim, Boehringer Ingelheim (Norway), University of Würzburg, Universitätsklinikum Würzburg, Berlin-Brandenburger Centrum für Regenerative Therapien, German Centre for Cardiovascular Research, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, Baylor University Medical Center, Imperial College London
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,300
Funders: Amgen, Eli Lilly and Company, AstraZeneca, Sanofi, Gilead Sciences, CSL Behring, Boston Scientific Corporation, LivaNova, Amarin Corporation, Cytokinetics, Impulse Dynamics, Moderna, Boehringer Ingelheim España, Deutsche Forschungsgemeinschaft, Novo Nordisk, Servier, Akebia Therapeutics, Abbott Vascular, Relypsa
OpenAlex ID: W4414240900