Treatment effects of empagliflozin in hospitalized heart failure patients across the range of left ventricular ejection fraction - Results from the EMPULSE trial

Jasper Tromp; Mikhail N Kosiborod; Christiane E Angermann; Sean P Collins; John R Teerlink; Piotr Ponikowski; Jan Biegus; João Pedro Ferreira; Michael E Nassif; Mitchell A Psotka; Martina Brueckmann; Jonathan P Blatchford; Dominik Steubl; Adriaan A Voors

doi:10.1002/ejhf.3218

Treatment effects of empagliflozin in hospitalized heart failure patients across the range of left ventricular ejection fraction - Results from the EMPULSE trial

Eur J Heart Fail. 2024 Apr 4. doi: 10.1002/ejhf.3218. Online ahead of print.

Authors

Jasper Tromp^{1

2}, Mikhail N Kosiborod^{3

4

5

6}, Christiane E Angermann⁷, Sean P Collins⁸, John R Teerlink⁹, Piotr Ponikowski¹⁰, Jan Biegus¹⁰, João Pedro Ferreira¹¹, Michael E Nassif^{3

4}, Mitchell A Psotka¹², Martina Brueckmann^{13

14}, Jonathan P Blatchford¹⁵, Dominik Steubl^{16

17}, Adriaan A Voors¹⁸

Affiliations

¹ Saw Swee Hock School of Public Health, National University of Singapore & the National University Health System, Singapore, Singapore.
² Duke-NUS Medical School, Singapore, Singapore.
³ Saint Luke's Mid America Heart Institute, Kansas City, MO, USA.
⁴ School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA.
⁵ George Institute for Global Health, Sydney, NSW, Australia.
⁶ University of New South Wales, Sydney, NSW, Australia.
⁷ Comprehensive Heart Failure Centre and Department of Medicine I (Cardiology), University and University Hospital of Würzburg, Würzburg, Germany.
⁸ Department of Emergency Medicine, Vanderbilt University Medical Center and Geriatric Research and Education Clinical Care, Tennessee Valley Healthcare Facility VA Medical Center, Nashville, TN, USA.
⁹ Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Institute of Heart Diseases, Medical University, Wroclaw, Poland.
¹¹ Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
¹² Inova Heart and Vascular Institute, Falls Church, VA, USA.
¹³ Boehringer Ingelheim International GmbH, Ingelheim, Germany.
¹⁴ First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁵ Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
¹⁶ Boehringer Ingelheim International, Ingelheim, Germany.
¹⁷ Department of Nephrology, Klinikum rechts der Isar, Faculty of Medicine, Technical University, Munich, Germany.
¹⁸ University of Groningen Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.

PMID: 38572654
DOI: 10.1002/ejhf.3218

Abstract

Aim: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium-glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF).

Methods and results: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41-49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all-cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41-49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], p_interaction = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint.

Conclusion: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in-hospital initiation of empagliflozin regardless of LVEF.

Keywords: Acute heart failure; Left ventricular ejection fraction; SGLT2 inhibitor.