title: Bleeding of new oral anticoagulants for stroke prevention in atrial fibrillation: a meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are new oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). We systematically reviewed their risk of major bleeding and efficacy in thromboembolism reduction in AF.
  
  
  METHODS
  Eligible randomized controlled trials evaluating NOACs for stroke prevention in AF patients were identified from a systematic search of MEDLINE, EMBASE and the Cochrane database. Risk ratios (RRs) and 95 % confidence intervals (CIs) were calculated using a Mantel-Haenzel random-effects model.
  
  
  RESULTS
  A total of 13 studies (n = 61,406) were included. Oral direct factor Xa inhibitors were more effective in reducing stroke and systemic embolism compared to controls (RR 0.71, 95 % CI 0.54-0.92, P = 0.009) or vitamin K antagonists (VKAs) (RR 0.84, 95 % CI 0.74-0.94, P = 0.002), with no significant difference in major and clinically relevant non-major (CRNM) bleeding (against controls: RR 0.94, 95 % CI 0.75-1.18, P = 0.60; against VKAs: RR 0.90, 95 % 0.69-1.17, P = 0.44). Oral direct thrombin inhibitors were associated with an improved major and CRNM bleeding profile (both comparisons: RR 0.88, 95 % CI 0.78-0.98, P = 0.02) and a significant reduction in stroke and systemic embolism (against controls: RR 0.79, 95 % CI 0.66-0.93, P = 0.006; against VKAs: RR 0.78, 95 % CI 0.66-0.93, P = 0.006).
  
  
  CONCLUSIONS
  Oral direct factor Xa inhibitors and oral direct thrombin inhibitors are more effective in reducing stroke and systemic embolism without increasing the risk of major bleeding compared to traditional oral anticoagulants. This favorable risk-benefit balance should be further confirmed by long-term, large-scale safety studies.
authors.affiliation: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, SH Ho Cardiovascular Disease and Stroke Centre, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR, China.
authors.forename: Joey S W
authors.initials: JS
authors.lastname: Kwong
authors.forename: Yat-Yin
authors.initials: YY
authors.lastname: Lam
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Yan
authors.forename: Cheuk-Man
authors.initials: CM
authors.lastname: Yu
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003627:Data Interpretation, Statistical; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors