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

Anker, SDORCID logo; Butler, J; Usman, MS; Filippatos, G; Ferreira, JP; Bocchi, E; Böhm, M; Rocca, HPB; Choi, D; Chopra, V; +25 more...Chuquiure, E; Giannetti, N; Gomez-Mesa, JE; Janssens, S; Januzzi, JLORCID logo; González-Juanatey, JR; Merkely, BORCID logo; Nicholls, SJ; Perrone, SV; Piña, ILORCID logo; Ponikowski, P; Senni, M; Sim, D; Spinar, J; Squire, I; Taddei, S; Tsutsui, H; Verma, S; Vinereanu, DORCID logo; Zhang, J; Iwata, T; Schnee, JM; Brueckmann, MORCID logo; Pocock, SJ; Zannad, FORCID logo and (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). pp. 2512-2520. ISSN 1078-8956 DOI: 10.1038/s41591-022-02041-5
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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.


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