Effects of dapagliflozin in DAPA-HF according to background heart failure therapy

DOI PDF 2 Citations
  • Kieran F Docherty
    BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA, UK
  • Pardeep S Jhund
    BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA, UK
  • Silvio E Inzucchi
    Section of Endocrinology, Yale University School of Medicine , 333 Cedar Street, New Haven, CT 06510 USA
  • Lars Køber
    Rigshospitalet Copenhagen University Hospital , Blegdamsvej 9, 2100 Copenhagen, Denmark
  • Mikhail N Kosiborod
    Saint Luke’s Mid America Heart Institute and University of Missouri-Kansas City , 4401 Wornall Road, Kansas City, MO 64111, USA
  • Felipe A Martinez
    National University of Cordoba , Av.Colon 2057, Cordoba X5003DSE, Argentina
  • Piotr Ponikowski
    Wroclaw Medical University , Borowska 213, Wroclaw 50-556, Poland
  • David L DeMets
    Department of Biostatistics & Medical Informatics, University of Wisconsin , 610 Walnut Street, 250 WARF, Madison, WI 53726, USA
  • Marc S Sabatine
    TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , 60 Fenwood Road, Boston, MA 02115 USA
  • Olof Bengtsson
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gothenburg, Pepparedsleden 1, Mölndal 431 83, Sweden
  • Mikaela Sjöstrand
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gothenburg, Pepparedsleden 1, Mölndal 431 83, Sweden
  • Anna Maria Langkilde
    Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gothenburg, Pepparedsleden 1, Mölndal 431 83, Sweden
  • Akshay S Desai
    Cardiovascular Division, Brigham and Women’s Hospital , 75 Francis Street, Boston, MA 02115, USA
  • Mirta Diez
    Division of Cardiology, Institute Cardiovascular de Buenos Aires , Av. Libertador 6302, C1428ART - Buenos Aires, Argentina
  • Jonathan G Howlett
    University of Calgary, Cardiac Sciences and Medicine , Room c838, 1403- 29th street NW, Calgary Alberta Canada, T2N2Y9
  • Tzvetana Katova
    Clinic of Cardiology, National Cardiology Hospital , 65 Konyovitsa Str., Sofia 1309, Bulgaria
  • Charlotta E A Ljungman
    Department of Molecular and Clinical Medicine and Cardiology , Sahlgrenska Academy, Gothenburg 413 45, Sweden
  • Eileen O’Meara
    Montreal Heart Institute, University of Montreal , 5000 Belanger, Montreal, Quebec H1T1C8, Canada
  • Mark C Petrie
    BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA, UK
  • Morten Schou
    Department of Cardiology, Gentofte University Hospital , Herlev Ringvej 75, 2730 Herlev, Denmark
  • Subodh Verma
    Division of Cardiac Surgery, St. Michael's Hospital, University of Toronto , 30 Bond Street, Toronto, Canada M5B 1W8
  • Pham Nguyen Vinh
    Department of Internal Medicine, Tan Tao University, Tan Duc Cardiology Hospital , No. 04 Nguyen Luong Bang, Tan Phu Ward, District 7, Ho Chi Minh City 70000, Vietnam
  • Scott D Solomon
    Cardiovascular Division, Brigham and Women’s Hospital , 75 Francis Street, Boston, MA 02115, USA
  • John J V McMurray
    BHF Cardiovascular Research Centre, University of Glasgow , 126 University Place, Glasgow G12 8TA, UK

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Aims</jats:title> <jats:p>In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and results</jats:title> <jats:p>In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and &lt;50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin–angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65–0.85] for the primary composite endpoint (P &lt; 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61–0.86) compared with 0.77 (95% CI 0.63–0.94) in those not on all three of these treatments (P-interaction 0.64).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The benefit of dapagliflozin was consistent regardless of background therapy for HF.</jats:p> </jats:sec>

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