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Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction
Scott D Solomon1, John J V McMurray1, Brian Claggett1
1From 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.).
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, like dapagliflozin, effectively reduce heart failure hospitalizations and cardiovascular death in patients with preserved ejection fraction. This study confirms their benefit in a broader heart failure population.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established treatments for heart failure with reduced ejection fraction.
- Efficacy of SGLT2 inhibitors in patients with higher left ventricular ejection fraction (LVEF) was less certain.
- This study investigated dapagliflozin in heart failure patients with LVEF > 40%.
Purpose of the Study:
- To evaluate the efficacy of dapagliflozin in patients with heart failure and mildly reduced or preserved ejection fraction.
- To assess the impact of dapagliflozin on worsening heart failure events and cardiovascular death in this population.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 6263 patients with LVEF > 40%.
- Patients received either dapagliflozin 10 mg daily or placebo, in addition to usual care.
- Primary outcome was a composite of worsening heart failure or cardiovascular death.
Main Results:
- Dapagliflozin significantly reduced the primary composite outcome (hazard ratio, 0.82; P<0.001).
- Worsening heart failure events were reduced by 21% (hazard ratio, 0.79; P<0.001).
- Benefits were consistent across subgroups, including those with and without diabetes, and across LVEF ranges (≥60% and <60%).
Conclusions:
- Dapagliflozin is effective in reducing the risk of worsening heart failure or cardiovascular death in patients with heart failure and mildly reduced or preserved ejection fraction.
- The findings support the use of SGLT2 inhibitors in a wider spectrum of heart failure patients.
- Adverse event rates were similar between dapagliflozin and placebo groups.
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