Empagliflozin, irrespective of blood pressure, improves outcomes in heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.

Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with HF and preserved ejection fraction. This study aims to evaluate if systolic blood pressure (SBP) moderates these effects. The association of SBP and the treatment effects of empagliflozin in EMPEROR-Preserved (empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction) was evaluated. Randomized patients (n 5988) were grouped according to SBP at baseline (110 mmHg, n 455; 110130 mmHg, n 2415; 130 mmHg, n 3118). The effect of empagliflozin on blood pressure, cardiovascular death or HF hospitalization (primary outcome), total HF hospitalizations, and rate of decline in estimated glomerular filtration rate was studied. Over a median of 26.2 months, the placebo-corrected decline was small and not significantly different across baseline SBP. On placebo, the risk of cardiovascular death or hospitalization for HF was 8.58 at 130 mmHg, 8.26 at 110130 mmHg, and 11.59 events per 100 patient-years at 110 mmHg (P 0.12 vs. 130 mmHg, P 0.08 vs. 110130 mmHg). There was no evidence for baseline SBP moderating the effect of empagliflozin on risk of HF events (primary endpoint interaction P 0.69, recurrent HF hospitalizations interaction P 0.55). When comparing empagliflozin with placebo, SBP did not meaningfully associate with adverse events such as hypotension, volume depletion, and acute renal failure. In EMPEROR-Preserved, empagliflozin was effective and safe without SBP meaningfully moderating empagliflozins treatment effects. This analysis of EMPEROR-Preserved shows that empagliflozin can be used safely and effectively without blood pressure being a meaningful moderator of the drug benefit. URL: https://www.clinicaltrials.gov Unique identifier: NCT03057951.

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The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Déclaration de conflit d'intérêts

Conflict of interest: M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322 900 939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, Recor, Servier, and Vifor during the conduct of the study. S.D.A reports grants and personal fees from Vifor Int. and Abbott Vascular, and personal fees from Astra-Zeneca, Bayer, Brahms, Boehringer Ingelheim, Cardiac Dimensions, Novartis, Occlutech, Servier, and Vifor Int. Personal fees from Boehringer Ingelheim during the conduct of the study. J.B. reports consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Ltd., and Vifor. Personal fees from Boehringer Ingelheim during the conduct of the study. J.P.F. reports consulting fees from Boehringer Ingelheim during the conduct of the study. G.F. reports Committee Member contributions in trials. Personal fees from Boehringer Ingelheim during the conduct of the study. F.M. reports grants and personal fees from Medtronic, personal fees from Recor, Boehringer Ingelheim and Berlin Chemie, outside the submitted work; L.L. reports speaker honoraria from Medtronic and ReCor Medical. S.P. reports personal fees from Boehringer Ingelheim during the conduct of the study. I.S. and M.B. are employees of Boehringer Ingelheim. E.S. is employee of mainanalytics, contracted by Boehringer Ingelheim. C.W. reports personal fees from Boehringer Ingelheim during the conduct of the study; personal fees from Akebia, AstraZeneca, Bayer, Eli Lilly, GSK, GILEAD, MSD, Mundipharma, Sanofi-Genzyme, and Vifor Fresenius outside the submitted work; F.Z. has received steering committee or advisory board fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cardior, CVRx, Janssen, Livanova, Merck, Mundipharma, Novartis, Novo Nordisk, and Vifor Fresenius. Personal fees from Boehringer Ingelheim during the conduct of the study. M.P. reports consulting fees from Boehringer Ingelheim, during the conduct of the study; consulting fees from Abbvie, Akcea, Amarin, AstraZeneca, Amgen, Boehringer Ingelheim, Cardiorentis, Daiichi Sankyo, Johnson Johnson, Lilly, Novartis, Pfizer, Relypsa, Sanofi, Synthetic Biologics, Theravance, NovoNordisk, outside the submitted work.