title: Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Subdural hematomas are an important bleeding complication of anticoagulation. We quantify the risk of subdural hematoma associated with anticoagulation with vitamin K antagonists (VKAs) compared with other oral antithrombotic therapies.
  
  
  METHODS
  Randomized trials were identified from the Cochrane Central Register of Controlled Trials and were included if published since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting oral anticoagulants. Two reviewers independently extracted data with differences resolved by joint review.
  
  
  RESULTS
  Nineteen randomized trials were included that involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were associated with a significantly increased risk of subdural hematoma (odds ratios, 3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9 trials, 11 603 participants). The risk of subdural hematoma was also significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of subdural hematoma among 24 485 patients with atrial fibrillation treated with VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95% confidence interval, 2.5-3.5) per 1000 patient-years.
  
  
  CONCLUSIONS
  VKA use significantly increases the risk of subdural hematoma by ≈3-fold relative to antiplatelet therapy. Direct-acting oral anticoagulants are associated with a significantly reduced risk of subdural hematomas versus VKAs. Based on indirect comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet monotherapies and factor Xa inhibitors.
authors.affiliation: From the Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (B.J.C., R.G.H.); and Biostatistics Consultant, Minot, ND (L.A.P.).
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Connolly
authors.affiliation: From the Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (B.J.C., R.G.H.); and Biostatistics Consultant, Minot, ND (L.A.P.).
authors.forename: Lesly A
authors.initials: LA
authors.lastname: Pearce
authors.affiliation: From the Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (B.J.C., R.G.H.); and Biostatistics Consultant, Minot, ND (L.A.P.). robert.hart@phri.ca.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D006408:Hematoma, Subdural / Q000139:chemically induced / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: anticoagulants; aspirin; hematoma, subdural; intracranial hemorrhages; warfarin