title: Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.
abstract: BACKGROUND
  Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting.
  
  
  RESULTS
  Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively.
  
  
  CONCLUSIONS
  Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients.
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.).
authors.forename: Peter Brønnum
authors.initials: PB
authors.lastname: Nielsen
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.).
authors.forename: Torben Bjerregaard
authors.initials: TB
authors.lastname: Larsen
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.).
authors.forename: Flemming
authors.initials: F
authors.lastname: Skjøth
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.).
authors.forename: Anders
authors.initials: A
authors.lastname: Gorst-Rasmussen
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.).
authors.forename: Lars Hvilsted
authors.initials: LH
authors.lastname: Rasmussen
authors.affiliation: From Department of Cardiology, Atrial Fibrillation Study group, Aalborg University Hospital, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Denmark (P.B.N., T.B.L., F.S., A.G.-R., L.H.R., G.Y.H.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, United Kingdom (G.Y.H.L.). g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications*; D002423:Cause of Death; D015897:Comorbidity; D016208:Databases, Factual; D003718:Denmark / Q000453:epidemiology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004617:Embolism / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D009026:Mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D019338:Polypharmacy; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors
keywords: anticoagulants; cerebral infarction; hemorrhage; stroke