title: Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis.
abstract: OBJECTIVE
  We performed a meta-analysis of data from randomized trials to estimate the risk of all-cause mortality and bleeding (and especially gastrointestinal [GI] bleeding) in patients treated with low doses of acetylsalicylic acid (ASA) (75-325 mg/d), alone or in combination with other medications.
  
  
  METHODS
  We searched 10 electronic databases (until October 2010) and collected data on adverse events in randomized controlled studies that evaluated low doses of ASA, alone (35 trials) or in combination with anticoagulants (18 trials), clopidogrel (5 trials), or proton pump inhibitors (PPIs; 3 trials). We analyzed data using random-effects meta-analysis and meta-regression, applying Peto's odds ratio (OR) for adverse events.
  
  
  RESULTS
  Low doses of ASA alone decreased the risk for all-cause mortality (relative risk, 0.93, 95% confidence interval [CI], 0.87-0.99), largely because of effects in secondary prevention populations. The risk of major GI bleeding increased with low doses of ASA alone (OR, 1.55; 95% CI, 1.27-1.90), compared with inert control reagents. The risk increased when ASA was combined with clopidogrel, compared with aspirin alone (OR, 1.86; 95% CI, 1.49-2.31), anticoagulants vs low doses of ASA alone (OR, 1.93; 95% CI, 1.42-2.61), or in studies that included patients with a history of GI bleeding or of longer duration. Importantly, PPI use reduced the risk for major GI bleeding in patients given low doses of ASA (OR, 0.34; 95% CI, 0.21-0.57).
  
  
  CONCLUSIONS
  In a meta-analysis, low doses of ASA increased the risk for GI bleeding; risk increased with accompanying use of clopidogrel and anticoagulant therapies, but decreased in patients who took PPIs.
authors.affiliation: Servicio de Aparato Digestivo, University of Zaragoza, IIS Aragón, CIBERehd, Spain. alanas@unizar.es
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Jennie
authors.initials: J
authors.lastname: Medin
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
mesh_terms: D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D001241:Aspirin