title: Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study.
abstract: BACKGROUND
  Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse.
  
  
  OBJECTIVE
  To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF.
  
  
  METHODS
  Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks.
  
  
  RESULTS
  Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%).
  
  
  CONCLUSIONS
  Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.
authors.forename: Laila
authors.initials: L
authors.lastname: Staerk
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen Ø, Denmark.|The Danish Heart Foundation, 1127 Copenhagen K, Denmark.
authors.forename: Emil Loldrup
authors.initials: EL
authors.lastname: Fosbøl
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK.
authors.forename: Gregory Y H
authors.initials: GYH
authors.lastname: Lip
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.|Department of Cardiology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen Ø, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Lamberts
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.
authors.forename: Anders Nissen
authors.initials: AN
authors.lastname: Bonde
authors.affiliation: Department of Cardiology and Clinical Epidemiology, Aalborg University Hospital and Department of Health, Science and Technology, Aalborg University, 9000 Aalborg, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Section of Biostatistics, Department of Public Health, University of Copenhagen, 1014 Copenhagen K, Denmark.
authors.forename: Brice
authors.initials: B
authors.lastname: Ozenne
authors.affiliation: Section of Biostatistics, Department of Public Health, University of Copenhagen, 1014 Copenhagen K, Denmark.
authors.forename: Thomas Alexander
authors.initials: TA
authors.lastname: Gerds
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.|The Danish Heart Foundation, 1127 Copenhagen K, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.|The National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen K, Denmark.
authors.forename: Gunnar Hilmar
authors.initials: GH
authors.lastname: Gislason
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Post 635, Kildegaardsvej 28, 2900 Hellerup, Denmark.|Department of Cardiology, Copenhagen University Hospital Hillerød, 3400 Hillerød, Denmark.
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications* / Q000453:epidemiology; D002545:Brain Ischemia / Q000139:chemically induced; D015331:Cohort Studies; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: Apixaban; Atrial fibrillation; Dabigatran; NOACs; Rivaroxaban; Stroke