Jawad H Butt1,2, Kieran F Docherty1, Pardeep S Jhund1, Rudolf A de Boer3, Michael Böhm4, Akshay S Desai5, Jonathan G Howlett6, Silvio E Inzucchi7, Mikhail N Kosiborod8, Felipe A Martinez9, Jose C Nicolau10, Mark C Petrie1, Piotr Ponikowski11, Olof Bengtsson12, Anna Maria Langkilde12, Morten Schou13, Mikaela Sjöstrand12, Scott D Solomon5, Marc S Sabatine5,14, John J V McMurray1, Lars Køber2. 1. British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 2. Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 3. Department of Cardiology, University Medical Center and University of Groningen, Groningen, The Netherlands. 4. Department of Internal Medicine III, Saarland University Hospital, Saarland University, Homburg, Germany. 5. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA. 6. Cumming School of Medicine and Libin Cardiovascular Institute, University of Calgary, Calgary, Canada. 7. Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA. 8. Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City; The George Institute for Global Health, University of New South Wales, Sydney, Australia. 9. Universidad Nacional de Córdoba, Córdoba, Argentina. 10. Instituto do Coracao (InCor), Hospital das Clínicas Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. 11. Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wrocław, Poland. 12. Late Stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 13. Department of Cardiology, Herlev-Gentofte University Hospital, Herlev, Denmark. 14. TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Abstract
AIMS: Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. METHODS AND RESULTS: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. CONCLUSIONS: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF.
AIMS: Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. METHODS AND RESULTS: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. CONCLUSIONS: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF.