Pooja Dewan1, Kieran F Docherty1, Olof Bengtsson2, Rudolf A de Boer3, Akshay S Desai4, Jaroslaw Drozdz5, Nathaniel M Hawkins6, Silvio E Inzucchi7, Masafumi Kitakaze8, Lars Køber9, Mikail N Kosiborod10, Anna Maria Langkilde2, Daniel Lindholm2, Felipe A Martinez11, Béla Merkely12, Mark C Petrie1, Piotr Ponikowski13, Marc S Sabatine14, Morten Schou15, Mikaela Sjöstrand2, Scott D Solomon4, Subodh Verma16, Pardeep S Jhund1, John J V McMurray1. 1. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. 2. Late Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 3. Department of Cardiology, University Medical Centre and University of Groningen, Groningen, The Netherlands. 4. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA. 5. Department of Cardiology, Medical University of Lodz, Lodz, Poland. 6. Division of Cardiology, University of British Columbia, Vancouver, Canada. 7. Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA. 8. Cardiovascular Division of Medicine, National Cerebral and Cardiovascular Centre, Osaka, Japan. 9. Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 10. Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, MO, USA. 11. National University of Cordoba, Cordoba, Argentina. 12. Heart and Vascular Centre, Semmelweis University, Budapest, Hungary. 13. Wroclaw Medical University, Wroclaw, Poland. 14. TIMI Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 15. Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark. 16. St Michael's Hospital, University of Toronto, Toronto, Canada.
Abstract
AIMS: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial. METHODS AND RESULTS: We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47]. CONCLUSIONS: In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03036124.
RCT Entities:
AIMS: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial. METHODS AND RESULTS: We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47]. CONCLUSIONS: In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03036124.
Authors: Leanne Mooney; Nathaniel M Hawkins; Pardeep S Jhund; Margaret M Redfield; Muthiah Vaduganathan; Akshay S Desai; Jean L Rouleau; Masatoshi Minamisawa; Amil M Shah; Martin P Lefkowitz; Michael R Zile; Dirk J Van Veldhuisen; Marc A Pfeffer; Inder S Anand; Aldo P Maggioni; Michele Senni; Brian L Claggett; Scott D Solomon; John J V McMurray Journal: J Am Heart Assoc Date: 2021-11-19 Impact factor: 6.106