title: Intracranial hemorrhage and subsequent ischemic stroke in patients with atrial fibrillation: a nationwide cohort study.
abstract: BACKGROUND
  The risk of ischemic stroke/thromboembolic events after an intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) who are on warfarin treatment is poorly characterized. The aim of this study was to assess the association between the risk of ischemic stroke/thromboembolic events and ICH.
  
  
  METHODS
  Linkage of three Danish nationwide administrative registries in the period between 1999 and 2012 identified patients with AF on warfarin treatment. Event-rate ratios of stroke/thromboembolic events, major bleeding, and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched OR was calculated for ICH occurrences within 0 to 3 months relative to the 3 to 6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated.
  
  
  RESULTS
  We studied 58,815 patients with AF (median age, 72.6 years; 60% men). When compared with the non-ICH group, the ICH group was at increased risk for stroke/systemic embolism/transient ischemic attack (TIA) (rate ratio, 3.67; 95% CI, 3.12-4.31) and mortality (rate ratio, 5.55; 95% CI, 5.20-5.92), but not for major bleeding (rate ratio, 1.06; 95% CI, 0.81-1.39). The matched OR of ICH occurrences prior to a stroke/systemic embolism/TIA was 4.33 (95% CI, 2.44-8.15). The rate ratio of claimed warfarin prescriptions post- and pre-ICH event was 0.28 (95% CI, 0.24-0.33).
  
  
  CONCLUSIONS
  In this large-scale study of patients with AF treated with warfarin, first-time ICH was associated with an increased rate of ischemic stroke/systemic embolism/TIA and mortality compared with the non-ICH group. There was a decrease in the warfarin-prescription purchase rate in the post-ICH period compared with pre-ICH, which may partly explain the excess risk.
authors.affiliation: Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Brønnum Nielsen
authors.affiliation: Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
authors.forename: Torben Bjerregaard
authors.initials: TB
authors.lastname: Larsen
authors.affiliation: Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Gorst-Rasmussen
authors.affiliation: Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Skjøth
authors.affiliation: Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
authors.forename: Lars Hvilsted
authors.initials: LH
authors.lastname: Rasmussen
authors.affiliation: Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark; University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, England. Electronic address: g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GYH
authors.lastname: Lip
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000453:epidemiology*; D015331:Cohort Studies; D015897:Comorbidity; D003718:Denmark / Q000453:epidemiology; D004617:Embolism / Q000453:epidemiology; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000150:complications* / Q000453:epidemiology*; D002546:Ischemic Attack, Transient / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D015996:Survival Rate; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin