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Original ArticleFree Preview

Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction

List of authors.
  • Scott D. Solomon, M.D.,
  • John J.V. McMurray, M.D.,
  • Brian Claggett, Ph.D.,
  • Rudolf A. de Boer, M.D.,
  • David DeMets, Ph.D.,
  • Adrian F. Hernandez, M.D.,
  • Silvio E. Inzucchi, M.D.,
  • Mikhail N. Kosiborod, M.D.,
  • Carolyn S.P. Lam, M.D.,
  • Felipe Martinez, M.D.,
  • Sanjiv J. Shah, M.D.,
  • Akshay S. Desai, M.D.,
  • Pardeep S. Jhund, M.B., Ch.B., Ph.D.,
  • Jan Belohlavek, M.D.,
  • Chern-En Chiang, M.D.,
  • C. Jan Willem Borleffs, M.D.,
  • Josep Comin-Colet, M.D., Ph.D.,
  • Dan Dobreanu, M.D.,
  • Jaroslaw Drozdz, M.D., Ph.D.,
  • James C. Fang, M.D.,
  • Marco Antonio Alcocer-Gamba, M.D.,
  • Waleed Al Habeeb, M.D.,
  • Yaling Han, M.D.,
  • Jose Walter Cabrera Honorio, M.D.,
  • Stefan P. Janssens, M.D.,
  • Tzvetana Katova, M.D.,
  • Masafumi Kitakaze, M.D.,
  • Béla Merkely, M.D., Ph.D.,
  • Eileen O’Meara, M.D.,
  • Jose Francisco Kerr Saraiva, M.D., Ph.D.,
  • Sergey N. Tereshchenko, M.D.,
  • Jorge Thierer, M.D.,
  • Muthiah Vaduganathan, M.D., M.P.H.,
  • Orly Vardeny, Pharm.D.,
  • Subodh Verma, M.D.,
  • Vinh Nguyen Pham, M.D.,
  • Ulrica Wilderäng, Ph.D.,
  • Natalia Zaozerska, M.D., Ph.D.,
  • Erasmus Bachus, M.D., Ph.D.,
  • Daniel Lindholm, M.D., Ph.D.,
  • Magnus Petersson, M.D., Ph.D.,
  • and Anna Maria Langkilde, M.D., Ph.D.
  • for the DELIVER Trial Committees and Investigators*



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.


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.


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.


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 number, NCT03619213.)

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Funding and Disclosures

Supported by AstraZeneca.

Disclosure forms provided by the authors are available with the full text of this article at

This article was published on August 27, 2022, at

A data sharing statement provided by the authors is available with the full text of this article at

Author Affiliations

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.).

Dr. Solomon can be contacted at or at the Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115.

A complete list of the DELIVER trial investigators is provided in the Supplementary Appendix, available at