title: Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.
abstract: BACKGROUND
  Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin.
  
  
  METHODS
  In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin.
  
  
  RESULTS
  Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43).
  
  
  CONCLUSIONS
  The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Elwood
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.|Hywel Dda University Health Board, Llanelli, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Morgan
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.|Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Julieta
authors.initials: J
authors.lastname: Galante
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: John W K
authors.initials: JW
authors.lastname: Chia
authors.affiliation: Institute of Cancer & Genetics Cardiff University, Cardiff, United Kingdom.
authors.forename: Sunil
authors.initials: S
authors.lastname: Dolwani
authors.affiliation: Harvard Medical School, Boston, MA, United States of America.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Graziano
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Kelson
authors.affiliation: University Clinic Hospital, University of Zaragoza, IIS Aragón, CIBEReshd, Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.affiliation: Welsh Institute for Health and Social Care, University of South Wales, Cardiff, United Kingdom.
authors.forename: Marcus
authors.initials: M
authors.lastname: Longley
authors.affiliation: Swansea Centre for Health Economics, Swansea University, Swansea, United Kingdom.
authors.forename: Ceri J
authors.initials: CJ
authors.lastname: Phillips
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Pickering
authors.affiliation: Medical School, Swansea University, Swansea, United Kingdom.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Roberts
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Singapore.
authors.forename: Swee S
authors.initials: SS
authors.lastname: Soon
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
authors.forename: Will
authors.initials: W
authors.lastname: Steward
authors.affiliation: University Library Services, Cardiff University, Cardiff, United Kingdom.
authors.forename: Delyth
authors.initials: D
authors.lastname: Morris
authors.affiliation: Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.|Specialist Unit for Review Evidence (SURE), Cardiff University, Cardiff, United Kingdom.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Weightman
mesh_terms: D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000150:complications / Q000188:drug therapy
chemical_list: D001241:Aspirin