Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes-Reference-Cited by-同舟云学术

Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes

Published:2020-12-22 Issue:6 Volume:42 Page:700-710
ISSN:0195-668X
Container-title:European Heart Journal
language:en
Short-container-title:

Author:

Abraham William T¹,Lindenfeld JoAnn²,Ponikowski Piotr³,Agostoni Piergiuseppe⁴⁵^ORCID,Butler Javed⁶,Desai Akshay S⁷,Filippatos Gerasimos⁸⁹^ORCID,Gniot Jacek¹⁰^ORCID,Fu Michael¹¹,Gullestad Lars¹²¹³¹⁴¹⁵,Howlett Jonathan G¹⁶^ORCID,Nicholls Stephen J¹⁷,Redon Josep¹⁸,Schenkenberger Isabelle¹⁹,Silva-Cardoso José²⁰,Störk Stefan²¹^ORCID,Krzysztof Wranicz Jerzy²²,Savarese Gianluigi²³^ORCID,Brueckmann Martina²⁴²⁵,Jamal Waheed²⁴^ORCID,Nordaby Matias²⁴^ORCID,Peil Barbara²⁶,Ritter Ivana²⁴^ORCID,Ustyugova Anastasia²⁴,Zeller Cordula²⁷^ORCID,Salsali Afshin²⁸,Anker Stefan D²⁹^ORCID

Affiliation:

1. Division of Cardiovascular Medicine, The Ohio State University, 473 West 12th Ave., Columbus, OH 43210, USA

2. Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA

3. Wroclaw Medical University, Wybrzeże L. Pasteura 1, 50-367, Wroclaw, Poland

4. Centro Cardiologico Monzino-IRCCS, Via Carlo Parea, 4 – 20138, Milan, Italy

5. Department of Clinical Sciences and Community Health, University of Milan, Via della Commenda 19 20122, Milan, Italy

6. Department of Medicine, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS-39216, USA

7. Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA

8. National and Kapodistrian University of Athens, School of Medicine, Athens 157 72, Greece

9. University of Cyprus, School of Medicine, Shacolas Educational Centre for Clinical Medicine, Palaios dromos Lefkosias Lemesou No.215/6, 2029 Aglantzia, Nicosia, Cyprus

10. Department of Cardiology, Independent Public Healthcare, General Hospital in Puławy; ul. Bema 1; 24 – 100 Pulawy, Poland

11. Section of Cardiology, Department of Medicine, Sahlgrenska University Hospital/Östra Hospital, Gothenburg University, Blå stråket 5, 413 45 Gothenburg, Sweden

12. Department of Cardiology, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway

13. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Søsterhjemmet, Kirkeveien 166, 2.etasje, 0450 Oslo, Norway

14. KG Jebsen Center for Cardiac Research, University of Oslo, Sogn Arena, Klaus Torgårds vei 3, 2. Etg, 0372 Oslo, Norway

15. Center for Heart Failure Research, Department of Cardiology Medicine (Building 3), 1st floor, Oslo University Hospital, Kirkeveien 166, 0407 Oslo, Norway

16. Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada

17. Monash Cardiovascular Research Centre, Monash University, 27 Rainforest Walk, Clayton VIC 3800, Melbourne, Australia

18. INCLIVA Research Institute, University of Valencia, vinguda de Menéndez y Pelayo, 4, 46010 Valencia, and CIBERObn, Madrid, Spain

19. Klinische Forschung Berlin GbR, Ansbacher Str. 17-19, 10787 Berlin, Germany

20. CardioCare, CINTESIS—Center for Health Technology and Services Research, and Director of the Cardiology Service, Porto University Medical School, São João University Medical Centre, Rua Dr. Plácido da Costa, s/n 4200-450, Porto, Portugal

21. Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, Würzburg University and University Hospital Würzburg, Straubmühlweg 2, 97078 Würzburg, Germany

22. Department of Electrocardiology, Medical University of Lodz, al. Tadeusza Kościuszki 4, 90-41, Lodz, Poland

23. Department of Medicine, Karolinska Institutet, Solna Karolinska University Hospital D1:04, SE-171 76 Stockholm, Sweden

24. Boehringer Ingelheim International GmbH, Binger Str. 173, 55216 Ingelheim am Rhein, Germany

25. Faculty of Medicine Mannheim, University of Heidelberg, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany

26. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, 55216 Ingelheim am Rhein, Germany

27. Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397 Biberach an der Riß, Germany

28. Heart Failure and DM Global Development, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Rd, Ridgefield, CT 06877, USA

29. Department of Cardiology (CVK), Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Föhrer Str. 15, 13353 Berlin, Germany

Abstract

Abstract Aims The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF). Methods and results HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (>40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were −4.0 m (−16.0, 6.0; P = 0.42) and 4.0 m (−5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported. Conclusion The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.

Funder

Boehringer Ingelheim

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

Link

http://academic.oup.com/eurheartj/article-pdf/42/6/700/36241281/ehaa943.pdf

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