Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

DOI Web Site 2 Citations
  • Alice M. Jackson
    BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.)
  • Pooja Dewan
    BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.)
  • Inder S. Anand
    Department of Cardiology, University of Minnesota, Minneapolis (I.S.A.).
  • Jan Bělohlávek
    2nd Department of Internal Medicine, Cardiovascular Medicine, General Teaching Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic (J.B.).
  • Olof Bengtsson
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D (O.B., A.M.L., D.L., M.S.), AstraZeneca, Gothenburg, Sweden.
  • Rudolf A. de Boer
    Department of Cardiology, University Medical Center and University of Groningen, The Netherlands (R.A.d.B.).
  • Michael Böhm
    Department of Medicine, Saarland University Hospital, Homburg–Saar, Germany (M.B.).
  • David W. Boulton
    Quantitative Clinical Pharmacology, IMED Biotech Unit, Astra-Zeneca, Gaithersburg, MD (D.W.B.).
  • Vijay K. Chopra
    Department of Cardiology, Medanta, Gurgaon, India (V.K.C.).
  • David L. DeMets
    Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison (D.L.D.).
  • Kieran F. Docherty
    BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.)
  • Andrej Dukát
    5th Department of Internal Medicine, Comenius University in Bratislava, Slovakia (A.D.).
  • Peter J. Greasley
    Cardiovascular, Renal and Metabolism Translational Medicines Unit, Early Clinical Development, IMED Biotech Unit (P.J.G.), AstraZeneca, Gothenburg, Sweden.
  • Jonathan G. Howlett
    Cumming School of Medicine and Libin Cardiovascular Institute, University of Calgary, AB, Canada (J.G.W.).
  • Silvio E. Inzucchi
    Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.).
  • Tzvetana Katova
    Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.).
  • Lars Køber
    Rigshospitalet Copenhagen University Hospital, Denmark (L.K.).
  • Mikhail N. Kosiborod
    Saint Luke’s Mid America Heart Institute, University of Missouri, Kansas City (M.N.K.).
  • Anna Maria Langkilde
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D (O.B., A.M.L., D.L., M.S.), AstraZeneca, Gothenburg, Sweden.
  • Daniel Lindholm
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D (O.B., A.M.L., D.L., M.S.), AstraZeneca, Gothenburg, Sweden.
  • Charlotta E.A. Ljungman
    Department of Molecular and Clinical Medicine and Cardiology, Sahlgrenska Academy, Gothenburg, Sweden (C.E.A.L.).
  • Felipe A. Martinez
    National University of Cordoba, Argentina (F.A.M.).
  • Eileen O’Meara
    Department of Cardiology, Montreal Heart Institute, QC, Canada (E.O.).
  • Marc S. Sabatine
    Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (M.S.S., S.D.S.).
  • Mikaela Sjöstrand
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D (O.B., A.M.L., D.L., M.S.), AstraZeneca, Gothenburg, Sweden.
  • Scott D. Solomon
    Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (M.S.S., S.D.S.).
  • Sergey Tereshchenko
    Department of Myocardial Disease and Heart Failure, National Medical Research Center of Cardiology, Moscow, Russia (S.T.).
  • Subodh Verma
    Division of Cardiac Surgery, St. Michael’s Hospital, University of Toronto, ON, Canada (S.V.).
  • Pardeep S. Jhund
    BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.)
  • John J.V. McMurray
    BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.)

Description

<jats:sec> <jats:title>Background:</jats:title> <jats:p>In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36–0.92), 0.83 (95% CI, 0.63–1.10), 0.77 (95% CI, 0.60–0.99), and 0.78 (95% CI, 0.63–0.97), respectively ( <jats:italic>P</jats:italic> for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68–0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF.</jats:p> </jats:sec> <jats:sec> <jats:title>Registration:</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov">https://www.clinicaltrials.gov</jats:ext-link> ; Unique identifier: NCT03036124. </jats:p> </jats:sec>

Journal

  • Circulation

    Circulation 142 (11), 1040-1054, 2020-09-15

    Ovid Technologies (Wolters Kluwer Health)

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