title: Extracranial arterial and venous thromboembolism in patients with atrial fibrillation: A meta-analysis of randomized controlled trials.
abstract: Thromboembolism prevention is central to atrial fibrillation (AF) management. Randomized controlled trials (RCTs) have primarily focused on stroke prevention. Detailed analyses of extracranial thromboembolic events, particularly in patients with low dose non-vitamin K antagonist oral anticoagulants (NOACs), are scarce.
  
  
  
  The purpose of this study was to assess efficacy of NOACs in prevention of extracranial arterial and venous thromboembolism.
  
  
  
  We searched PubMed, CENTRAL, and CINAHL through April 2016 for phase III RCTs of NOACs in patients with AF. Information regarding systemic embolism (SE), pulmonary embolism (PE), and deep vein thrombosis (DVT) was retrieved and compared by risk ratio (RR) and 95% confidence interval (CI) with a fixed-effects model. A network with additional RCTs involving antiplatelet agents was constructed. The surface under the cumulative ranking curve (SUCRA) of each treatment was calculated for assessing the best treatment in the network meta-analysis.
  
  
  
  Among 72,963 patients with AF from 5 RCTs, relative to warfarin, standard dose NOACs were associated with a lower risk of SE (RR 0.71, 95% CI 0.52-0.99) and similar risks of PE and DVT (RR 0.95, 95% CI 0.72-1.35; and RR 0.83, 95% CI 0.56-1.24, respectively). Compared with warfarin, risks of SE, PE, and DVT with low dose NOACs were similar. In network meta-analyses, standard dose NOACs were associated with the largest SUCRA for prevention of SE and PE.
  
  
  
  In patients with AF, standard dose NOACs were the most efficacious treatment in preventing SE, whereas both dose regimens of NOACs were reasonable alternatives to warfarin in preventing venous thromboembolism.
authors.affiliation: General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: klwang2@vghtpe.gov.tw.
authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Wang
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
authors.affiliation: Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.affiliation: School of Nursing, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Institute of Information Science, Academia Sinica, Taipei, Taiwan.
authors.forename: En-Yu
authors.initials: EY
authors.lastname: Lai
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chern-En
authors.initials: CE
authors.lastname: Chiang
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D000925:Anticoagulants / Q000145:classification / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D006801:Humans; D011655:Pulmonary Embolism / Q000209:etiology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000209:etiology / Q000517:prevention & control
chemical_list: D000925:Anticoagulants
keywords: Anticoagulant; Atrial fibrillation; Cardiovascular outcomes; Systemic embolism; Venous thromboembolism