title: Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial.
abstract: BACKGROUND
  Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood.
  
  
  METHODS
  We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors.
  
  
  RESULTS
  COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p=0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p<0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p=0.617).
  
  
  CONCLUSIONS
  COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA; Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA. Electronic address: michael.durheim@duke.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Durheim
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Derek D
authors.initials: DD
authors.lastname: Cyr
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA; Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Laine E
authors.initials: LE
authors.lastname: Thomas
authors.affiliation: Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Tsuang
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA; Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA; Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA; Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004617:Embolism / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: Anticoagulation; Atrial fibrillation; COPD; Mortality; Stroke