title: Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation.
abstract: BACKGROUND
  In the last 4 years, four novel oral anticoagulants have been developed as alternatives to warfarin and antiplatelet agents for stroke prevention in atrial fibrillation (AF) patients. The objective of this review was to estimate the comparative effectiveness of all antithrombotic treatments for AF patients.
  
  
  METHODS
  Data sources were Medline Ovid (1946 to October 2015), Embase Ovid (1980 to October 2015), and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 9, 2015). Randomized controlled trials of AF patients were selected if they compared at least two of the following: placebo, aspirin, aspirin and clopidogrel combination therapy, adjusted-dose warfarin (target international normalized ratio 2.0-3.0), dabigatran, rivaroxaban, apixaban, and edoxaban. Bayesian network meta-analyses were conducted for outcomes of interest (all stroke, ischemic stroke, myocardial infarction, overall mortality, major bleeding, and intracranial hemorrhage).
  
  
  RESULTS
  Based on 16 randomized controlled trials of 96,826 patients, all oral anticoagulants were more effective than antiplatelet agents at reducing the risk of ischemic stroke and all strokes. Compared to warfarin, dabigatran 150 mg (rate ratio 0.65, 95% credible interval 0.52-0.82) and apixaban (rate ratio 0.82, 95% credible interval 0.69-0.97) reduced the risk of all strokes. Dabigatran 150 mg was also more effective than warfarin at reducing ischemic stroke risk (rate ratio 0.76, 95% credible interval 0.59-0.99). Aspirin, apixaban, dabigatran 110 mg, and edoxaban were associated with less major bleeding than warfarin.
  
  
  CONCLUSIONS
  All oral anticoagulants reduce the risk of stroke in AF patients. Some novel oral anticoagulants are associated with a lower stroke and/or major bleeding risk than warfarin. In addition to the safety and effectiveness of drug therapy, as reported in this study, individual treatment recommendations should also consider the patient's underlying stroke and bleeding risk profile.
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy; Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto.
authors: Amy
authors: A
authors: Tawfik
authors: Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto.
authors: Joanna M
authors: JM
authors: Bielecki
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy; Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto.
authors: Murray
authors: M
authors: Krahn
authors: Centre for Excellence in Economic Analysis Research (CLEAR), Li Ka Shing Knowledge Institute, St Michael's Hospital; Department of Medicine and Cardiology, University of Toronto.
authors: Paul
authors: P
authors: Dorian
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy; Centre for Excellence in Economic Analysis Research (CLEAR), Li Ka Shing Knowledge Institute, St Michael's Hospital; Pharmacoeconomics Research Unit, Cancer Care Ontario, Toronto, ON.
authors: Jeffrey S
authors: JS
authors: Hoch
authors: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy.
authors: Heather
authors: H
authors: Boon
authors: Institute of Health Economics, Edmonton, AB, Canada.
authors: Don
authors: D
authors: Husereau
authors: Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto.
authors: Petros
authors: P
authors: Pechlivanoglou
keywords: atrial fibrillation/prevention and control; cerebrovascular disorders/drug therapy; meta-analysis; platelet-aggregation inhibitors; stroke prevention