title: Nonvitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin.
  
  
  METHODS
  We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies.
  
  
  RESULTS
  Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139).
  
  
  CONCLUSIONS
  In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.
authors.affiliation: Department of Medicine, University of Thessaly, Biopolis 41110, Larissa, Greece. gntaios@med.uth.gr
authors.forename: George
authors.initials: G
authors.lastname: Ntaios
authors.forename: Vasileios
authors.initials: V
authors.lastname: Papavasileiou
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Makaritsis
authors.forename: Patrik
authors.initials: P
authors.lastname: Michel
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage*; D001596:Benzylamines / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D014812:Vitamin K; C426686:ximelagatran; D014859:Warfarin