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 Piña; Piotr 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

doi:10.1038/s41591-022-02041-5

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	2512–2520
Number of pages	18
Journal	Nature Medicine
Volume	28
Issue number	12
Early online date	5 Dec 2022
DOIs	https://doi.org/10.1038/s41591-022-02041-5
Publication status	Published - 9 Dec 2022

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Cite this

Anker, S. D., Butler, J., Usman, M. S., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., Rocca, H. P. B.-L., Choi, D.-J., Chopra, V., Chuquiure, E., Giannetti, N., Gomez-Mesa, J. E., Janssens, S., Januzzi, J. L., González-Juanatey, J. R., Merkely, B., Nicholls, S. J., Perrone, S. V., ... Zannad, F. (2022). Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved. Nature Medicine, 28(12), 2512–2520. https://doi.org/10.1038/s41591-022-02041-5

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

abstract = "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.",

author = "Anker, {Stefan D} and Javed Butler and Usman, {Muhammad Shariq} and Gerasimos Filippatos and Ferreira, {Jo{\~a}o Pedro} and Edimar Bocchi and Michael B{\"o}hm and Rocca, {Hans Pieter Brunner-La} and Dong-Ju Choi and Vijay Chopra and Eduardo Chuquiure and Nadia Giannetti and Gomez-Mesa, {Juan Esteban} and Stefan Janssens and Januzzi, {James L} and Gonz{\'a}lez-Juanatey, {Jos{\'e} R} and Bela Merkely and Nicholls, {Stephen J} and Perrone, {Sergio V} and Pi{\~n}a, {Ileana L} and Piotr Ponikowski and Michele Senni and David Sim and Jindrich Spinar and Iain Squire and Stefano Taddei and Hiroyuki Tsutsui and Subodh Verma and Dragos Vinereanu and Jian Zhang and Tomoko Iwata and Schnee, {Janet M} and Martina Brueckmann and Pocock, {Stuart J} and Faiez Zannad",

note = "{\textcopyright} 2022. The Author(s).",

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doi = "10.1038/s41591-022-02041-5",

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Anker, SD, Butler, J, Usman, MS, Filippatos, G, Ferreira, JP, Bocchi, E, Böhm, M, Rocca, HPB-L, Choi, D-J, Chopra, V, Chuquiure, E, Giannetti, N, Gomez-Mesa, JE, Janssens, S, Januzzi, JL, González-Juanatey, JR, Merkely, B, Nicholls, SJ, Perrone, SV, Piña, IL, Ponikowski, P, Senni, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Iwata, T, Schnee, JM, Brueckmann, M, Pocock, SJ & Zannad, F 2022, 'Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved', Nature Medicine, vol. 28, no. 12, pp. 2512–2520. https://doi.org/10.1038/s41591-022-02041-5

TY - JOUR

T1 - Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction

T2 - a pre-specified analysis of EMPEROR-Preserved

AU - Anker, Stefan D

AU - Butler, Javed

AU - Usman, Muhammad Shariq

AU - Filippatos, Gerasimos

AU - Ferreira, João Pedro

AU - Bocchi, Edimar

AU - Böhm, Michael

AU - Rocca, Hans Pieter Brunner-La

AU - Choi, Dong-Ju

AU - Chopra, Vijay

AU - Chuquiure, Eduardo

AU - Giannetti, Nadia

AU - Gomez-Mesa, Juan Esteban

AU - Janssens, Stefan

AU - Januzzi, James L

AU - González-Juanatey, José R

AU - Merkely, Bela

AU - Nicholls, Stephen J

AU - Perrone, Sergio V

AU - Piña, Ileana L

AU - Ponikowski, Piotr

AU - Senni, Michele

AU - Sim, David

AU - Spinar, Jindrich

AU - Squire, Iain

AU - Taddei, Stefano

AU - Tsutsui, Hiroyuki

AU - Verma, Subodh

AU - Vinereanu, Dragos

AU - Zhang, Jian

AU - Iwata, Tomoko

AU - Schnee, Janet M

AU - Brueckmann, Martina

AU - Pocock, Stuart J

AU - Zannad, Faiez

PY - 2022/12/9

Y1 - 2022/12/9

N2 - 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.

AB - 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.

U2 - 10.1038/s41591-022-02041-5

DO - 10.1038/s41591-022-02041-5

M3 - Article

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SN - 1078-8956

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JO - Nature Medicine

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