Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved

Stefan D. Anker, Javed Butler, Muhammad Shariq Usman, Gerasimos Filippatos, João Pedro Ferreira, Edimar Bocchi, Michael Böhm, Hans Pieter Brunner La Rocca, Dong Ju Choi, Vijay Chopra, Eduardo Chuquiure, Nadia Giannetti, Juan Esteban Gomez-Mesa, Stefan Janssens, James L. Januzzi, José R. González-Juanatey, Bela Merkely, Stephen J. Nicholls, Sergio V. Perrone, Ileana L. PiñaPiotr Ponikowski, Michele Senni, David Sim, Jindrich Spinar, Iain Squire, Stefano Taddei, Hiroyuki Tsutsui, Subodh Verma, Dragos Vinereanu, Jian Zhang, Tomoko Iwata, Janet M. Schnee, Martina Brueckmann, Stuart J. Pocock, Faiez Zannad

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10 Citations (Scopus)


The EMPEROR-Preserved trial showed that the sodium–glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41–49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71–0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66–1.04, P = 0.11). For patients with an LVEF of 41–49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57–0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42–0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.

Original languageEnglish
Pages (from-to)2512-2520
Number of pages9
JournalNature medicine
Issue number12
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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