Scott D Solomon1, John J V McMurray1, Brian Claggett1, Rudolf A de Boer1, David DeMets1, Adrian F Hernandez1, Silvio E Inzucchi1, Mikhail N Kosiborod1, Carolyn S P Lam1, Felipe Martinez1, Sanjiv J Shah1, Akshay S Desai1, Pardeep S Jhund1, Jan Belohlavek1, Chern-En Chiang1, C Jan Willem Borleffs1, Josep Comin-Colet1, Dan Dobreanu1, Jaroslaw Drozdz1, James C Fang1, Marco Antonio Alcocer-Gamba1, Waleed Al Habeeb1, Yaling Han1, Jose Walter Cabrera Honorio1, Stefan P Janssens1, Tzvetana Katova1, Masafumi Kitakaze1, Béla Merkely1, Eileen O'Meara1, Jose Francisco Kerr Saraiva1, Sergey N Tereshchenko1, Jorge Thierer1, Muthiah Vaduganathan1, Orly Vardeny1, Subodh Verma1, Vinh Nguyen Pham1, Ulrica Wilderäng1, Natalia Zaozerska1, Erasmus Bachus1, Daniel Lindholm1, Magnus Petersson1, Anna Maria Langkilde1. 1. From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston (S.D.S., B.C., A.S.D., M.V.); the British Heart Foundation Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, United Kingdom (J.J.V.M., P.S.J.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen (R.A.B., C.S.P.L.), and Haga Teaching Hospital, the Hague (C.J.W.B.) - both in the Netherlands; the University of Wisconsin, Madison (D. DeMets); Duke University Medical Center, Durham, NC (A.F.H.); Yale School of Medicine, New Haven, CT (S.E.I.); Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, Kansas City (M.N.K.); National Heart Center Singapore and Duke-National University of Singapore, Singapore (C.S.P.L.); National University of Cordoba, Cordoba (F.M.), and Jefe de Unidad de Insuficiencia Cardíaca, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, Buenos Aires (J.T.) - both in Argentina; Northwestern University Feinberg School of Medicine, Chicago (S.J.S.); General University Hospital, Charles University, Prague, Czech Republic (J.B.); General Clinical Research Center and the Division of Cardiology, Taipei Veterans General Hospital and National Yang Ming Chiao Tung University, Taipei, Taiwan (C.-E.C.); the Department of Cardiology, Bellvitge University Hospital and Bellvitge Biomedical Research Institute, University of Barcelona, L'Hospitalet de Llobregat, Barcelona (J.C.-C.); George Emil Palade University of Medicine, Pharmacy, Science, and Technology, Târgu Mureş, Romania (D. Dobreanu); the Department of Cardiology, Medical University Lodz, Lodz, Poland (J.D.); University of Utah Medical Center, Salt Lake City (J.C.F.); Centro de Estudios Clínicos de Querétaro, Querétaro, Mexico (M.A.A.-G.); the Cardiac Sciences Department, King Saud University, Riyadh, Saudi Arabia (W.A.H.); the Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China (Y.H.); Clínica Vesalio, San Borja, Peru (J.W.C.H.); the Department of Cardiovascular Diseases, Cardiac Intensive Care, University Hospitals Leuven, Leuven, Belgium (S.P.J.); the Department of Noninvasive Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.); Kinshukai Hanwa Daini Senboku Hospital, Osaka, Japan (M.K.); Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Institut de Cardiologie de Montréal, Université de Montréal, Montreal (E.O.), and the Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto (S.V.) - both in Canada; the Cardiovascular Division, Instituto de Pesquisa Clínica de Campinas, Campinas, Brazil (J.F.K.S.); the Department of Myocardial Disease and Heart Failure, National Medical Research Center of Cardiology, Moscow (S.N.T.); the Minneapolis Veterans Affairs Center for Care Delivery and Outcomes Research, University of Minnesota, Minneapolis (O.V.); Cardiovascular Center, Tam Anh Hospital, Tan Tao University, Tan Duc, Vietnam (V.N.P.); and Late-Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (U.W., N.Z., E.B., D.L., M.P., A.M.L.).
Abstract
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. METHODS: We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction. (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.).
Authors: Akshay S Desai; Pardeep S Jhund; Brian L Claggett; Muthiah Vaduganathan; Zi Michael Miao; Toru Kondo; Ebrahim Barkoudah; Abdel Brahimi; Eugene Connolly; Peter Finn; Ninian N Lang; Finnian R Mc Causland; Martina McGrath; Mark C Petrie; John J V McMurray; Scott D Solomon Journal: JAMA Cardiol Date: 2022-10-03 Impact factor: 30.154
Authors: Muthiah Vaduganathan; Brian L Claggett; Pardeep Jhund; Rudolf A de Boer; Adrian F Hernandez; Silvio E Inzucchi; Mikhail N Kosiborod; Carolyn S P Lam; Felipe Martinez; Sanjiv J Shah; Akshay S Desai; Sheila M Hegde; Daniel Lindholm; Magnus Petersson; Anna Maria Langkilde; John J V McMurray; Scott D Solomon Journal: JAMA Cardiol Date: 2022-10-03 Impact factor: 30.154
Authors: Carlos Escobar; Beatriz Palacios; Luis Varela; Martín Gutiérrez; Mai Duong; Hungta Chen; Nahila Justo; Javier Cid-Ruzafa; Ignacio Hernández; Phillip R Hunt; Juan F Delgado Journal: J Clin Med Date: 2022-09-02 Impact factor: 4.964
Authors: Carlos Escobar; Beatriz Palacios; Luis Varela; Martín Gutiérrez; Mai Duong; Hungta Chen; Nahila Justo; Javier Cid-Ruzafa; Ignacio Hernández; Phillip R Hunt; Juan F Delgado Journal: BMC Health Serv Res Date: 2022-10-08 Impact factor: 2.908