title: Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation.
abstract: OBJECTIVE
  To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.
  
  
  METHODS
  Systematic review and network meta-analysis.
  
  
  METHODS
  A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.
  
  
  METHODS
  Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.
  
  
  RESULTS
  For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.
  
  
  CONCLUSIONS
  Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.
  PROSPERO registry-CRD42012002721.
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Chris
authors.identifier: http://orcid.org/0000-0003-3613-760X
authors.initials: C
authors.lastname: Cameron
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Coyle
authors.affiliation: Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Richter
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada.
authors.forename: Kasandra
authors.initials: K
authors.lastname: Gauthier
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Steiner
authors.affiliation: Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Applied Health Economics Research Unit, Ottawa, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Coyle
authors.affiliation: Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Bai
authors.affiliation: Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada.
authors.forename: Kristen
authors.initials: K
authors.lastname: Moulton
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada.
authors.forename: Tammy
authors.initials: T
authors.lastname: Clifford
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Wells
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D020521:Stroke / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents
keywords: CARDIOLOGY; EPIDEMIOLOGY