Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation.

Javed Butler, Milton Packer, Gerasimos Filippatos, Tomoko Iwata, Dimitrios Farmakis, Stuart J Pocock, Faiez Zannad, João Pedro Ferreira, Anne Pernille Ofstad, Martina Brueckmann, Stefan D Anker

Journal: European journal of heart failure 2023;25(7):970-977

PMID: 37062866

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Abstract

AIMS

Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.

METHODS AND RESULTS

In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66-0.93] vs. 0.78 [0.64-0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57-0.94] vs. 0.72 [0.54-0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m /year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.

CONCLUSIONS

In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.

Address: National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.; University of Cyprus Medical School, Nicosia, Cyprus.; Baylor Scott and White Research Institute, Dallas, TX, USA.; Department of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA.; Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Nancy, France.; Cardiovascular R&D Centre - UnIC@RISE, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of Porto, Porto, Portugal.; Medical Department, Boehringer Ingelheim Norway KS, Asker, Norway.; Oslo Diabetes Research Center, Oslo, Norway.; Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.; Boehringer Ingelheim International GmbH, Ingelheim, Germany.; First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.; Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.; Baylor University Medical Center, Dallas, TX, USA.; Imperial College, London, UK.; Department of Cardiology (CVK) of German Heart Center Charité; Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany.

DOI: 10.1002/ejhf.2861