title: Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.
abstract: BACKGROUND
  Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes.
  
  
  METHODS
  We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality.
  
  
  RESULTS
  Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS2and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P<.0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P<.0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia.
  
  
  CONCLUSIONS
  Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, Netherlands. Electronic address: b.d.westenbrink@umcg.nl.
authors.forename: B Daan
authors.initials: BD
authors.lastname: Westenbrink
authors.affiliation: Working Group on Cardiovascular Research, Utrecht, Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Alings
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Boston University School of Medicine, Boston, MA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Wojdyla
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Hungarian Institute of Cardiology, Budapest, Hungary.
authors.forename: Matyas
authors.initials: M
authors.lastname: Keltai
authors.affiliation: DHU FIRE, Université Paris-Diderot, Hôpital Bichat, AP-HP, INSERM, Paris, France.
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: G. d'Annunzio Univ and Fondazione Toscana G. Monasterio, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000453:epidemiology*; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D004617:Embolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin