EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)

Summary

The aim of the study is to investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

Timeline

Start

2017-03-06

Primary completion

2020-05-01

Completion

2020-05-28

Publications

• Packer M, Ferreira JP, Butler J, Filippatos G, Januzzi JL Jr, Gonzalez Maldonado S, Panova-Noeva M, Pocock SJ, Prochaska JH, Saadati M, Sattar N, Sumin M, Anker SD, Zannad F. Reaffirmation of Mechanistic Proteomic Signatures Accompanying SGLT2 Inhibition in Patients With Heart Failure: A Validation Cohort of the EMPEROR Program. J Am Coll Cardiol. 2024 Nov 12;84(20):1979-1994. doi: 10.1016/j.jacc.2024.07.013. Epub 2024 Aug 31.
• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.
• Talha KM, Green J, Filippatos G, Pocock S, Zannad F, Brueckmann M, Schueler E, Ofstad AP, Ferreira JP, Anker SD, Butler J, Rosenstock J, Packer M. Impact of empagliflozin on insulin needs in patients with heart failure and diabetes: An EMPEROR-Pooled analysis. Diabetes Obes Metab. 2024 Jul;26(7):2578-2587. doi: 10.1111/dom.15572. Epub 2024 Apr 1.
• Ferreira JP, Packer M, Sattar N, Butler J, Pocock SJ, Anker SD, Maldonado SG, Panova-Noeva M, Sumin M, Masson S, Zannad F, Januzzi JL. Carbohydrate antigen 125 concentrations across the ejection fraction spectrum in chronic heart failure: The EMPEROR programme. Eur J Heart Fail. 2024 Apr;26(4):788-802. doi: 10.1002/ejhf.3166. Epub 2024 Mar 4.
• Ferreira JP, Butler J, Anker SD, Januzzi JL, Panova-Noeva M, Reese-Petersen AL, Sattar N, Schueler E, Pocock SJ, Filippatos G, Packer M, Sumin M, Zannad F; EMPEROR Committees and Investigators. Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials. Eur J Heart Fail. 2024 Feb;26(2):274-284. doi: 10.1002/ejhf.3101. Epub 2023 Dec 28.
• Zannad F, Macari S. Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Future Cardiol. 2023 Oct;19(13):625-630. doi: 10.2217/fca-2023-0090. Epub 2023 Nov 9.
• Dhingra NK, Verma S, Butler J, Anker SD, Ferreira JP, Filippatos G, Januzzi JL, Lam CSP, Sattar N, Zaremba-Pechmann L, Bohm M, Nordaby M, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Reduced Trial Committees and Investigators. Efficacy and Safety of Empagliflozin According to Background Diuretic Use in HFrEF: Post-Hoc Analysis of EMPEROR-Reduced. JACC Heart Fail. 2024 Jan;12(1):35-46. doi: 10.1016/j.jchf.2023.06.036. Epub 2023 Sep 13.
• Packer M, Butler J, Zeller C, Pocock SJ, Brueckmann M, Ferreira JP, Filippatos G, Usman MS, Zannad F, Anker SD. Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure. Circulation. 2023 Sep 26;148(13):1011-1022. doi: 10.1161/CIRCULATIONAHA.123.065748. Epub 2023 Aug 24.
• Carson P, Teerlink JR, Komajda M, Anand I, Anker SD, Butler J, Doehner W, Ferreira JP, Filippatos G, Haass M, Miller A, Pehrson S, Pocock SJ, Schnaidt S, Schnee JM, Zannad F, Packer M. Comparison of Investigator-Reported and Centrally Adjudicated Heart Failure Outcomes in the EMPEROR-Reduced Trial. JACC Heart Fail. 2023 Apr;11(4):407-417. doi: 10.1016/j.jchf.2022.11.017. Epub 2023 Feb 1.
• Khan MS, Butler J, Anker SD, Filippatos G, Ferreira JP, Pocock SJ, Januzzi JL, Pina IL, Bohm M, Ponikowski P, Verma S, Brueckmann M, Vedin O, Zeller C, Zannad F, Packer M. Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause. J Am Heart Assoc. 2023 Jan 3;12(1):e027652. doi: 10.1161/JAHA.122.027652. Epub 2022 Dec 24.
• Ferreira JP, Zannad F, Butler J, Filippatos G, Pocock SJ, Brueckmann M, Steubl D, Schueler E, Anker SD, Packer M. Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure: A Secondary Analysis of EMPEROR-Pooled. JAMA Cardiol. 2022 Nov 1;7(11):1148-1159. doi: 10.1001/jamacardio.2022.2924.
• Zannad F, Ferreira JP, Butler J, Filippatos G, Januzzi JL, Sumin M, Zwick M, Saadati M, Pocock SJ, Sattar N, Anker SD, Packer M. Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme. Eur Heart J. 2022 Dec 21;43(48):4991-5002. doi: 10.1093/eurheartj/ehac495.
• Zannad F, Ferreira JP, Gregson J, Kraus BJ, Mattheus M, Hauske SJ, Butler J, Filippatos G, Wanner C, Anker SD, Pocock SJ, Packer M; EMPEROR-Reduced Trial Committees and Investigators. Early changes in estimated glomerular filtration rate post-initiation of empagliflozin in EMPEROR-Reduced. Eur J Heart Fail. 2022 Oct;24(10):1829-1839. doi: 10.1002/ejhf.2578. Epub 2022 Jul 7.
• Ferreira JP, Zannad F, Butler J, Filipattos G, Ritter I, Schuler E, Kraus BJ, Pocock SJ, Anker SD, Packer M. Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled. Eur Heart J. 2022 Aug 14;43(31):2984-2993. doi: 10.1093/eurheartj/ehac306.
• Ferreira JP, Butler J, Zannad F, Filippatos G, Schueler E, Steubl D, Zeller C, Januzzi JL, Pocock S, Packer M, Anker SD. Mineralocorticoid Receptor Antagonists and Empagliflozin in Patients With Heart Failure and Preserved Ejection Fraction. J Am Coll Cardiol. 2022 Mar 29;79(12):1129-1137. doi: 10.1016/j.jacc.2022.01.029.
• Ferreira JP, Anker SD, Butler J, Filippatos G, Iwata T, Salsali A, Zeller C, Pocock SJ, Zannad F, Packer M. Impact of anaemia and the effect of empagliflozin in heart failure with reduced ejection fraction: findings from EMPEROR-Reduced. Eur J Heart Fail. 2022 Apr;24(4):708-715. doi: 10.1002/ejhf.2409. Epub 2022 Jan 9.
• Verma S, Dhingra NK, Butler J, Anker SD, Ferreira JP, Filippatos G, Januzzi JL, Lam CSP, Sattar N, Peil B, Nordaby M, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Reduced trial committees and investigators. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial. Lancet Diabetes Endocrinol. 2022 Jan;10(1):35-45. doi: 10.1016/S2213-8587(21)00292-8. Epub 2021 Nov 30.
• Ryden L, Ferrannini G. Is the impact of add on heart failure therapy influenced by background therapy? Lancet Diabetes Endocrinol. 2022 Jan;10(1):3-5. doi: 10.1016/S2213-8587(21)00311-9. Epub 2021 Nov 30. No abstract available.
• Bohm M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Mahfoud F, Brueckmann M, Jamal W, Ofstad AP, Schuler E, Ponikowski P, Wanner C, Zannad F, Packer M; EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure. J Am Coll Cardiol. 2021 Sep 28;78(13):1337-1348. doi: 10.1016/j.jacc.2021.07.049.
• Januzzi JL Jr, Zannad F, Anker SD, Butler J, Filippatos G, Pocock SJ, Ferreira JP, Sattar N, Verma S, Vedin O, Schnee J, Iwata T, Cotton D, Packer M; EMPEROR-Reduced Trial Committees and Investigators. Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial. J Am Coll Cardiol. 2021 Sep 28;78(13):1321-1332. doi: 10.1016/j.jacc.2021.07.046.
• Packer M, Butler J, Zannad F, Filippatos G, Ferreira JP, Pocock SJ, Carson P, Anand I, Doehner W, Haass M, Komajda M, Miller A, Pehrson S, Teerlink JR, Schnaidt S, Zeller C, Schnee JM, Anker SD. Effect of Empagliflozin on Worsening Heart Failure Events in Patients With Heart Failure and Preserved Ejection Fraction: EMPEROR-Preserved Trial. Circulation. 2021 Oct 19;144(16):1284-1294. doi: 10.1161/CIRCULATIONAHA.121.056824. Epub 2021 Aug 29.
• Pocock SJ, Ferreira JP, Gregson J, Anker SD, Butler J, Filippatos G, Gollop ND, Iwata T, Brueckmann M, Januzzi JL, Voors AA, Zannad F, Packer M. Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial. Eur Heart J. 2021 Nov 14;42(43):4455-4464. doi: 10.1093/eurheartj/ehab579.
• Lam CSP, Ferreira JP, Pfarr E, Sim D, Tsutsui H, Anker SD, Butler J, Filippatos G, Pocock SJ, Sattar N, Verma S, Brueckmann M, Schnee J, Cotton D, Zannad F, Packer M. Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial. Eur Heart J. 2021 Nov 14;42(43):4442-4451. doi: 10.1093/eurheartj/ehab360.
• Ferreira JP, Zannad F, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Jamal W, Steubl D, Schueler E, Packer M. Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure: EMPEROR-Reduced. J Am Coll Cardiol. 2021 Mar 23;77(11):1397-1407. doi: 10.1016/j.jacc.2021.01.044.
• Packer M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Sattar N, Brueckmann M, Jamal W, Cotton D, Iwata T, Zannad F; EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload: EMPEROR-Reduced Trial. J Am Coll Cardiol. 2021 Mar 23;77(11):1381-1392. doi: 10.1016/j.jacc.2021.01.033.
• Butler J, Anker SD, Filippatos G, Khan MS, Ferreira JP, Pocock SJ, Giannetti N, Januzzi JL, Pina IL, Lam CSP, Ponikowski P, Sattar N, Verma S, Brueckmann M, Jamal W, Vedin O, Peil B, Zeller C, Zannad F, Packer M; EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial. Eur Heart J. 2021 Mar 31;42(13):1203-1212. doi: 10.1093/eurheartj/ehaa1007.
• Anker SD, Butler J, Filippatos G, Khan MS, Marx N, Lam CSP, Schnaidt S, Ofstad AP, Brueckmann M, Jamal W, Bocchi EA, Ponikowski P, Perrone SV, Januzzi JL, Verma S, Bohm M, Ferreira JP, Pocock SJ, Zannad F, Packer M. Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status: Results From the EMPEROR-Reduced Trial. Circulation. 2021 Jan 26;143(4):337-349. doi: 10.1161/CIRCULATIONAHA.120.051824. Epub 2020 Nov 11.
• Zannad F, Ferreira JP, Pocock SJ, Zeller C, Anker SD, Butler J, Filippatos G, Hauske SJ, Brueckmann M, Pfarr E, Schnee J, Wanner C, Packer M. Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights From EMPEROR-Reduced. Circulation. 2021 Jan 26;143(4):310-321. doi: 10.1161/CIRCULATIONAHA.120.051685. Epub 2020 Oct 23.
• Packer M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Carson P, Anand I, Doehner W, Haass M, Komajda M, Miller A, Pehrson S, Teerlink JR, Brueckmann M, Jamal W, Zeller C, Schnaidt S, Zannad F. Effect of Empagliflozin on the Clinical Stability of Patients With Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial. Circulation. 2021 Jan 26;143(4):326-336. doi: 10.1161/CIRCULATIONAHA.120.051783. Epub 2020 Oct 21.
• Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28.
• Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.

Drugs

Indications