Stefan D Anker1, Javed Butler1, Gerasimos Filippatos1, João P Ferreira1, Edimar Bocchi1, Michael Böhm1, Hans-Peter Brunner-La Rocca1, Dong-Ju Choi1, Vijay Chopra1, Eduardo Chuquiure-Valenzuela1, Nadia Giannetti1, Juan Esteban Gomez-Mesa1, Stefan Janssens1, James L Januzzi1, Jose R Gonzalez-Juanatey1, Bela Merkely1, Stephen J Nicholls1, Sergio V Perrone1, Ileana L Piña1, Piotr Ponikowski1, Michele Senni1, David Sim1, Jindrich Spinar1, Iain Squire1, Stefano Taddei1, Hiroyuki Tsutsui1, Subodh Verma1, Dragos Vinereanu1, Jian Zhang1, Peter Carson1, Carolyn Su Ping Lam1, Nikolaus Marx1, Cordula Zeller1, Naveed Sattar1, Waheed Jamal1, Sven Schnaidt1, Janet M Schnee1, Martina Brueckmann1, Stuart J Pocock1, Faiez Zannad1, Milton Packer1. 1. From the Department of Cardiology (CVK) and the Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Center for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin (S.D.A.), Universitätsklinikum des Saarlandes, Homberg (M. Böhm), RWTH Aachen University, Aachen (N.M.), Boehringer Ingelheim Pharma, Biberach (C.Z., S.S.), Boehringer Ingelheim International, Ingelheim (W.J., M. Brueckmann), and the Faculty of Medicine Mannheim, University of Heidelberg, Mannheim (M. Brueckmann) - all in Germany; the University of Mississippi Medical Center, Jackson (J.B.); National and Kapodistrian University of Athens School of Medicine, Athens (G.F.); Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, and INSERM Unité 1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) (J.P.F.), and Université de Lorraine, INSERM INI-CRCT, CHRU (F.Z.) - both in Nancy, France; the Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal (J.P.F.); Unidade de Insuficiência Cardíaca, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo (E.B.); Maastricht University Medical Center and the School for Cardiovascular Disease CARIM - both in Maastricht, the Netherlands (H.-P.B.-L.R.); the Department of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea (D.-J.C.); Max Superspeciality Hospital, Saket, New Delhi, India (V.C.); the National Institute of Cardiology, Mexico City (E.C.-V.); McGill University Health Centre, Montreal (N.G.), and St. Michael's Hospital, University of Toronto, Toronto (S.V.) - both in Canada; the Cardiology Service, Fundación Valle del Lili, Universidad Icesi, Cali, Colombia (J.E.G.-M.); the Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium (S.J.); Massachusetts General Hospital and Baim Institute for Clinical Research, Boston (J.L.J.); University Hospital, Santiago de Compostela, Spain (J.R.G.-J.); Heart and Vascular Center, Semmelweiss University, Budapest, Hungary (B.M.); Victorian Heart Institute, Monash University, Melbourne, VIC, Australia (S.J.N.); Argentine Catholic University, and Medical Advisor in Heart Failure, Pulmonary Hypertension and Intrathoracic Transplant at FLENI and IADT Institute - both in Buenos Aires (S.V.P.); Central Michigan University, Mount Pleasant (I.L.P.); Wroclaw Medical University, Wroclaw, Poland (P.P.); the Cardiovascular Department, Cardiology Division, Papa Giovanni XXIII Hospital, Bergamo (M.S.), and Università di Pisa, Pisa (S.T.) - both in Italy; National Heart Centre Singapore, Singapore (D.S.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the University of Leicester, Glenfield General Hospital, Leicester (I.S.), the University of Glasgow, Glasgow (N.S.), the London School of Hygiene and Tropical Medicine (S.J.P.), and Imperial College, London (M.P.) - all in the United Kingdom; Kyushu University, Fukuoka, Japan (H.T.); the University of Medicine and Pharmacy, Carol Davila University and Emergency Hospital, Bucharest, Romania (D.V.); the Heart Failure Center, Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing (J.Z.); the Veterans Affairs Medical Center, Washington, DC (P.C.); National Heart Centre Singapore, Duke-National University of Singapore, Singapore (C.S.P.L.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (J.M.S.); and Baylor Heart and Vascular Institute, Dallas (M.P.).
Abstract
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).
Authors: Archana Rai; Kim A Connelly; Subodh Verma; C David Mazer; Hwee Teoh; Ming-Yen Ng; Idan Roifman; Adrian Quan; Marina Pourafkari; Laura Jimenez-Juan; Venkat Ramanan; Yin Ge; Djeven P Deva; Andrew T Yan Journal: Acta Diabetol Date: 2022-01-21 Impact factor: 4.280