title: Risk of major bleeding in patients receiving vitamin K antagonists or low doses of aspirin. A systematic review and meta-analysis.
abstract: Prior meta-analysis and observational studies have suggested that the bleeding risks associated with anticoagulation using vitamin K antagonists (VKA) or aspirin (ASA) are similar.
  
  
  OBJECTIVE
  The aim of this systematic review was to provide the odds ratios (ORs) of major bleeding, intracranial bleeding or major extra-cranial bleeding of anticoagulation with VKA compared to low doses of ASA.
  
  
  METHODS
  We conducted a systematic review of Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (RCT). Randomized controlled trials reporting bleeding rates in adult patients randomized to a VKA (INR 2-3) or to ASA alone (<325mg daily). Random effects OR were calculated.
  
  
  RESULTS
  Fifteen trials reporting the outcome of 2511 participants treated with VKA alone and 2471 treated with ASA alone were included; most common conditions evaluated were non-valvular atrial fibrillation (five trials) and heart failure (three trials). Overall, the use of VKA was associated with an increased risk of major bleeding (OR 1.76 (95% CI 1.33-2.33) when compared to ASA. The OR associated with VKA use for intracranial bleeding and extra-cranial bleeding were 1.74 (95% CI 0.83-3.62) and 1.66 (95% CI 0.94-2.92), respectively. In trials achieving good control of anticoagulation [time in therapeutic range (TTR) >65%], the risk of bleeding with VKA was similar to that of ASA [OR 1.16 (95% CI 0.79-1.71)].
  
  
  CONCLUSIONS
  Contrary to prior reports our results suggest that the risk of major bleeding with the use VKA is higher compared to those of patients treated with ASA alone. However, in patients achieving a good TTR, the risk of major bleeding with VKA or ASA is similar.
authors.affiliation: Internal Medicine Research Unit, Internal Medicine Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Internal Medicine Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Vazquez
authors.affiliation: Hospital Universitario, Universidad Nacional de Cuyo, Mendoza, Argentina.
authors.forename: Joaquín P
authors.initials: JP
authors.lastname: Gonzalez
authors.affiliation: Thrombosis Program, Division of Hematology-Department of Medicine, University of Ottawa-Ottawa Hospital, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Gregoire
authors.initials: G
authors.lastname: LeGal
authors.affiliation: Thrombosis Program, Division of Hematology-Department of Medicine, University of Ottawa-Ottawa Hospital, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Thrombosis Program, Division of Hematology-Department of Medicine, University of Ottawa-Ottawa Hospital, Ottawa, Canada; Ottawa Hospital Research Institute, Ottawa, Canada. Electronic address: egandara@ohri.ca.
authors.forename: Esteban
authors.initials: E
authors.lastname: Gándara
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000453:epidemiology; D016017:Odds Ratio; D018570:Risk Assessment; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014812:Vitamin K; D001241:Aspirin