title: Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials.
abstract: OBJECTIVE
  The relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2-3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial.
  
  
  METHODS
  In this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4<INR<3.5) for the prevention of arterial thrombosis with a minimum of three month follow-up and of 50 patients per treatment arm. The outcome measures were major bleedings and intracranial bleedings.
  
  
  RESULTS
  Ten eligible trials including 9047 patients were included, 451 of whom experienced major bleedings and 62 had intracranial bleeding. The 10 studies were homogeneous in spite of different clinical settings, including atrial fibrillation, heart failure and cerebral ischemia from arterial origin. Mean achieved INR on VKA varied from to 2.1 to 2.6. Compared with VKA, aspirin had an overall lower major bleeding risk (relative risk=0.58; 95% CI: 0.46-0.75; p<0.001). There was a non-significant trend for a lower intracranial bleeding risk on aspirin versus VKA (relative risk=0.65; 95% CI: 0.40-1.06; p=0.09).
  
  
  CONCLUSIONS
  Major bleeding risk is substantially lower on aspirin than on VKA targeting current usual INR range. Physicians should take into account this data when choosing between different antithrombotic regimens.
authors.affiliation: Department of Therapeutics, Hôpital de la Timone, 13385 Marseille, France; Department of Cardiology, Hôpital de la Timone, 13385 Marseille, France. Electronic address: pierre.ambrosi@ap-hm.fr.
authors.forename: P
authors.initials: P
authors.lastname: Ambrosi
authors.affiliation: Department of Therapeutics, Hôpital de la Timone, 13385 Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Daumas
authors.affiliation: Department of Therapeutics, Hôpital de la Timone, 13385 Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Villani
authors.affiliation: Aix-Marseille Université, UMR_S 912 (SESSTIM), IRD, 13385 Marseille, France; INSERM, UMR_S 912 (SESSTIM), 13385 Marseille, France; APHM, hôpital Timone, Service Biostatistique et Technologies de l'Information et de la Communication, 13005 Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Giorgi
mesh_terms: D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D014943:Global Health; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013927:Thrombosis / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014812:Vitamin K; D001241:Aspirin
keywords: Aspirin; Bleeding; Meta-analysis; Vitamin K antagonists; Warfarin