title: Major bleeding in patients with atrial fibrillation receiving vitamin K antagonists: a systematic review of randomized and observational studies.
abstract: OBJECTIVE
  Clinical trials have shown that anticoagulation with vitamin K antagonists (VKAs), e.g. warfarin, decreases the risk of stroke in patients with atrial fibrillation (AF); however, increased bleeding risk is one of the safety concerns. The primary objective was to conduct a systematic review of the published literature, assessing the risk of major bleeding and mortality in patients with AF treated with VKAs.
  
  
  RESULTS
  Online searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative follow-up was 61,563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9-3.4 per 100 patient-years) for RCTs and 2.0 per 100 patient-years (range, 0.2-7.6 per 100 patient-years) for observational studies. With study year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing over time was noted. Mortality rates from observational studies were inadequately reported to allow comparison with those from RCT data.
  
  
  CONCLUSIONS
  The median rate of major bleeding in observational studies and RCTs is similar. The larger heterogeneity in bleeding rates observed in a real-life setting could reflect a high variability in standard of care of patients on VKAs and/or methodological differences between observational studies and/or variability in data sources.
authors: RTI Health Solutions, 2nd Floor, The Pavilion, Towers Business Park, Wilmslow Road, Didsbury, Manchester M20 2LS, UK. nroskell@rti.org
authors: Neil S
authors: NS
authors: Roskell
authors: Miny
authors: M
authors: Samuel
authors: Herbert
authors: H
authors: Noack
authors: Brigitta U
authors: BU
authors: Monz
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality*; D015897:Comorbidity; D019317:Evidence-Based Medicine; D006470:Hemorrhage / Q000401:mortality*; D006801:Humans; D015994:Incidence; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D013923:Thromboembolism / Q000401:mortality* / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: Atrial fibrillation; Bleeding; Mortality; Observational studies; Randomized studies; Systematic review