Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure.

Background: Empagliflozin reduces the risk of cardiovascular death or heart failure (HF) hospitalization in patients with reduced ejection fraction. Its interplay with systolic blood pressure (SBP) is not known.
Objectives: The goal of this study was to evaluate the interplay of SBP and the effects of empagliflozin in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).
Methods: Study patients (N = 3,730) were randomly assigned to groups according to SBP at baseline (<110 mm Hg, n = 928; 110-130 mm Hg, n = 1,755; >130 mm Hg, n = 1,047). This study explored the influence of SBP on the effects of empagliflozin on cardiovascular death or HF hospitalization (primary outcome), as well as on total HF hospitalizations, rate of decline in estimated glomerular filtration rate, renal outcomes, and empagliflozin's effects and significance on SBP.
Results: Over a median of 16 months considering only patients receiving placebo, baseline SBP and the risk of cardiovascular death or hospitalization for HF (P trend = 0.0015) were inversely related. Corrected for placebo, a slight early increase was observed in SBP at <110 mm Hg, no change at 110-130 mm Hg, and a slight reduction at >130 mm Hg. These between-group differences were of borderline significance (P for interaction trend = 0.05-0.10) after 4 and 12 weeks but were not significant later. SBP at baseline did not influence the effect of empagliflozin to reduce the risk of HF events or renal endpoints. When treated with empagliflozin, patients with SBP <110 mm Hg did not have an increased rate of symptomatic hypotension.
Conclusions: Empagliflozin was effective and safe, with no meaningful interaction between SBP and the effects of empagliflozin in the EMPEROR-Reduced trial. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
Competing Interests: Funding Support and Author Disclosures All authors were involved in the EMPEROR trial, which was funded by Boehringer Ingelheim and Eli Lilly. Dr Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939); and has received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier, and Vifor during the conduct of the study. Dr Anker has received grants and personal fees from Vifor Int and Abbott Vascular; has received personal fees from Bayer, Brahms GmbH, Boehringer Ingelheim, Cardiac Dimensions, Cordio, Novartis, and Servier; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Butler has received consulting fees from Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, BerlinCures, Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, Occlutech, and Vifor; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Ferreira has received consulting fees from Boehringer Ingelheim during the conduct of the study. Dr Filippatos reports Committee Member contributions in trials; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Mahfoud has received grants and personal fees from Medtronic; and has received personal fees from ReCor, Boehringer Ingelheim, and Berlin Chemie, outside the submitted work. Dr Pocock has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Ponikowski has received personal fees from Boehringer Ingelheim, AstraZeneca, Servier, BMS, Amgen, Novartis, Merck, Pfizer, and Berlin Chemie; and has received grants and personal fees from Vifor Pharma. Drs Ofstad, Jamal, and Brueckmann are employees of Boehringer Ingelheim. Dipl Math Schüler is an employee of mainanalytics, contracted by Boehringer Ingelheim. Dr Wanner has received personal fees from Boehringer Ingelheim during the conduct of the study; and has received personal fees from Akebia, AstraZeneca, Bayer, Eli Lilly, GSK, Gilead, MSD, Mundipharma, Sanofi-Genzyme, and Vifor Fresenius outside the submitted work. Dr Zannad 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; and has received personal fees from Boehringer Ingelheim during the conduct of the study. Dr Packer has received consulting fees from Boehringer Ingelheim during the conduct of the study; and has received consulting fees from Abbvie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Casana, CSL Behring, Cytokinetics, Johnson & Johnson, Eli Lily & Company, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, and Theravance, outside the submitted work.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)