title: Aspirin in primary prevention of cardiovascular disease and cancer: a systematic review of the balance of evidence from reviews of randomized trials.
abstract: BACKGROUND
  Aspirin has been recommended for primary prevention of cardiovascular disease (CVD) and cancer, but overall benefits are unclear. We aimed to use novel methods to re-evaluate the balance of benefits and harms of aspirin using evidence from randomised controlled trials, systematic reviews and meta-analyses.
  
  
  RESULTS
  Data sources included ten electronic bibliographic databases, contact with experts, and scrutiny of reference lists of included studies. Searches were undertaken in September 2012 and restricted to publications since 2008. Of 2,572 potentially relevant papers 27 met the inclusion criteria. Meta-analysis of control arms to estimate event rates, modelling of all-cause mortality and L'Abbé plots to estimate heterogeneity were undertaken. Absolute benefits and harms were low: 60-84 major CVD events and 34-36 colorectal cancer deaths per 100,000 person-years were averted, whereas 46-49 major bleeds and 68-117 gastrointestinal bleeds were incurred. Reductions in all-cause mortality were minor and uncertain (Hazard Ratio 0.96; 95% CI: 0.90-1.02 at 20 years, Relative Risk [RR] 0.94, 95% CI: 0.88-1.00 at 8 years); there was a non-significant change in total CVD (RR 0.85, 95% CI: 0.69-1.06) and change in total cancer mortality ranged from 0.76 (95% CI: 0.66-0.88) to 0.93 (95% CI: 0.84-1.03) depending on follow-up time and studies included. Risks were increased by 37% for gastrointestinal bleeds (RR 1.37, 95% CI: 1.15-1.62), 54%-66% for major bleeds (Rate Ratio from IPD analysis 1.54, 95% CI: 1.30-1.82, and RR 1.62, 95% CI: 1.31-2.00), and 32%-38% for haemorrhagic stroke (Rate Ratio from IPD analysis 1.32; 95% CI: 1.00-1.74; RR 1.38; 95% CI: 1.01-1.82).
  
  
  CONCLUSIONS
  Findings indicate small absolute effects of aspirin relative to the burden of these diseases. When aspirin is used for primary prevention of CVD the absolute harms exceed the benefits. Estimates of cancer benefit rely on selective retrospective re-analysis of RCTs and more information is needed.
authors: Warwick Medical School, University of Warwick, Coventry, Warwickshire, England.
authors: Paul
authors: P
authors: Sutcliffe
authors: Martin
authors: M
authors: Connock
authors: Tara
authors: T
authors: Gurung
authors: Karoline
authors: K
authors: Freeman
authors: Samantha
authors: S
authors: Johnson
authors: Kandala
authors: K
authors: Ngianga-Bakwin
authors: Amy
authors: A
authors: Grove
authors: Binu
authors: B
authors: Gurung
authors: Sarah
authors: S
authors: Morrow
authors: Saverio
authors: S
authors: Stranges
authors: Aileen
authors: A
authors: Clarke
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000517:prevention & control*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin