title: Effects of dabigatran according to age in atrial fibrillation.
abstract: The prevalence of atrial fibrillation (AF) and the risk of stroke and bleeding vary according to age. To estimate effects of dabigatran, compared with warfarin, on stroke, bleeding and mortality in patients with AF in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial according to age, we analysed treatment effects using age as a continuous variable and using age categories.
  
  
  
  RE-LY included 10 855 (59.9%) patients aged <75 years, 4231 patients (23.4%) aged 75-79 years, 2305 (12.7%) aged 80-84 years and 722 (4.0%) aged ≥85 years at baseline.
  
  
  
  Benefits of dabigatran versus warfarin regarding stroke (HR range 0.63 (95% CI 0.46 to 0.86) to 0.70 (0.31 to 1.57) for dabigatran 150 mg twice daily), HR range 0.52 (0.21 to 1.29) to 1.08 (0.73 to 1.60) for dabigatran 110 mg twice daily) and intracranial bleeding were maintained across all age groups (interaction p values all not significant). There was a highly significant interaction (p value interaction <0.001) between age and treatment for extracranial major bleeding, with lower rates with both doses of dabigatran compared with warfarin in younger patients (HR 0.78 (0.62 to 0.97) for 150 mg twice daily, HR 0.72 (0.57 to 0.90) for 110 mg twice daily) but similar (HR 1.50 (1.03 to 2.18) for 110 mg twice daily) or higher rates (HR 1.68 (1.18 to 2.41) for 150 mg twice daily) in older patients (≥80 years).
  
  
  
  Effects of dabigatran compared with warfarin on stroke prevention and intracranial bleeding are consistent across all age groups. Effects of dabigatran on extracranial major bleeding are age dependent, supporting selection of dabigatran 110 mg twice daily for elderly patients (age ≥80 years).
  
  
  
  Clinical trial registration number: https://clinicaltrials.gov NCT00262600.
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.|Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mandy N
authors.initials: MN
authors.lastname: Lauw
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.|Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Coppens
authors.affiliation: Department of Medical Sciences, Clinical Research Center, University of Uppsala, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Jefferson Medical College and Lankenau Medical Center, Philadelphia, Pennsylvania, USA.|Cardiovascular Research Foundation, New York, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ezekowitz
authors.affiliation: Department of Medical Sciences, Clinical Research Center, University of Uppsala, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Juliet
authors.initials: J
authors.lastname: Nakamya
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, Ontario, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D000069604:Dabigatran / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D009864:Ontario / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate / Q000639:trends; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Age; atrial fibrillation; bleeding; dabigatran etexilate; ischaemic stroke; warfarin