Li Shen1, Søren Lund Kristensen2, Olof Bengtsson3, Michael Böhm4, Rudolf A de Boer5, Kieran F Docherty6, Silvio E Inzucchi7, Tzvetana Katova8, Lars Køber9, Mikhail N Kosiborod10, Anna Maria Langkilde3, Daniel Lindholm3, M Felipe A Martinez11, Eileen O'Meara12, Jose C Nicolau13, Mark C Petrie6, Piotr Ponikowski14, Marc S Sabatine15, Morten Schou16, Mikaela Sjöstrand3, Scott D Solomon17, Pardeep S Jhund6, John J V McMurray18. 1. Department of Medicine, Hangzhou Normal University, Hangzhou, China; BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. 2. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark. 3. AstraZeneca R & D, Gothenburg, Sweden. 4. Klinik für Innere Medizin III, Universität des Saarlandes, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany. 5. Department of Cardiology, University Medical Center and University of Groningen, Groningen, the Netherlands. 6. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. 7. Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA. 8. Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria. 9. Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark. 10. Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri, USA. 11. National University of Cordoba, Cordoba, Argentina. 12. Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. 13. Instituto do Coracao (InCor), Hospital das Clínicas Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. 14. Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland. 15. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 16. Department of Cardiology, Gentofte University Hospital Copenhagen, Copenhagen, Denmark. 17. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA. 18. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.mcmurray@glasgow.ac.uk.
Abstract
OBJECTIVES: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. BACKGROUND: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. METHODS: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. RESULTS: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. CONCLUSIONS: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
OBJECTIVES: The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. BACKGROUND: MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. METHODS: A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. RESULTS: A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. CONCLUSIONS: Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
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Authors: Peter Rossing; Gerasimos Filippatos; Rajiv Agarwal; Stefan D Anker; Bertram Pitt; Luis M Ruilope; Juliana C N Chan; Adriaan Kooy; Kieran McCafferty; Guntram Schernthaner; Christoph Wanner; Amer Joseph; Markus F Scheerer; Charlie Scott; George L Bakris Journal: Kidney Int Rep Date: 2021-10-14
Authors: Michele Provenzano; Niels Jongs; Priya Vart; Bergur V Stefánsson; Glenn M Chertow; Anna Maria Langkilde; John J V McMurray; Ricardo Correa-Rotter; Peter Rossing; C David Sjöström; Robert D Toto; David C Wheeler; Hiddo J L Heerspink Journal: Kidney Int Rep Date: 2021-12-14