William T Abraham1, JoAnn Lindenfeld2, Piotr Ponikowski3, Piergiuseppe Agostoni4,5, Javed Butler6, Akshay S Desai7, Gerasimos Filippatos8,9, Jacek Gniot10, Michael Fu11, Lars Gullestad12,13,14,15, Jonathan G Howlett16, Stephen J Nicholls17, Josep Redon18, Isabelle Schenkenberger19, José Silva-Cardoso20, Stefan Störk21, Jerzy Krzysztof Wranicz22, Gianluigi Savarese23, Martina Brueckmann24,25, Waheed Jamal24, Matias Nordaby24, Barbara Peil26, Ivana Ritter24, Anastasia Ustyugova24, Cordula Zeller27, Afshin Salsali28, Stefan D Anker29. 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
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 FailureQuestionnaire 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. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Gabriele G Schiattarella; Pilar Alcaide; Gianluigi Condorelli; Thomas G Gillette; Stephane Heymans; Elizabeth A V Jones; Marinos Kallikourdis; Andrew Lichtman; Federica Marelli-Berg; Sanjiv Shah; Edward B Thorp; Joseph A Hill Journal: Nat Cardiovasc Res Date: 2022-03-14
Authors: Moritz J Hundertmark; Olorunsola F Agbaje; Ruth Coleman; Jyothis T George; Rolf Grempler; Rury R Holman; Hanan Lamlum; Jisoo Lee; Joanne E Milton; Heiko G Niessen; Oliver Rider; Christopher T Rodgers; Ladislav Valkovič; Eleanor Wicks; Masliza Mahmod; Stefan Neubauer Journal: ESC Heart Fail Date: 2021-05-06
Authors: Matteo Pagnesi; Luca Baldetti; Alberto Aimo; Riccardo Maria Inciardi; Daniela Tomasoni; Enrico Vizzardi; Giuseppe Vergaro; Michele Emdin; Carlo Mario Lombardi Journal: J Clin Med Date: 2022-01-11 Impact factor: 4.241