title: Validity of composite outcomes in meta-analyses of stroke prevention trials: the case of aspirin.
abstract: BACKGROUND
  Aspirin has been reported to be less effective for secondary vascular prevention in patients with ischaemic stroke, compared with other high-risk populations. This contention is largely based on results of meta-analyses that used a composite outcome of vascular death, myocardial infarction and stroke, reporting a 13% relative risk reduction. In this study, we explore whether the summary relative risk reduction for this composite outcome is representative of estimates for each of the individual components of the composite.
  
  
  METHODS
  All randomised controlled trials comparing aspirin with placebo/control in patients following ischaemic stroke or transient ischaemic attack, beyond the acute period (2 weeks).
  
  
  METHODS
  A fixed-effects model was used and summary risk ratios were calculated for each of the outcomes: vascular mortality, recurrent non-fatal stroke, non-fatal myocardial infarction, composite of the latter three outcomes, all-cause mortality and non-vascular mortality.
  
  
  RESULTS
  Ten trials (n = 9,168) were included. For the composite of non-fatal stroke, non-fatal myocardial infarction and vascular death, aspirin was associated with a 13% reduction in risk (risk ratio, RR: 0.87; 95% CI: 0.81-0.94). For individual components of the composite, aspirin reduced the risk of non-fatal ischaemic stroke (RR: 0.81; 95% CI: 0.72-0.90) and non-fatal myocardial infarction (RR: 0.68; 95% CI: 0.52-0.87), but not vascular death (RR: 0.97; 95% CI: 0.86-1.1). Aspirin did reduce the risk of non-vascular death (RR: 0.79; 95% CI: 0.66-0.95), though, and had a trend towards a reduced risk of all-cause mortality (RR: 0.91; 95% CI: 0.81-1.01).
  
  
  CONCLUSIONS
  Following ischaemic stroke, aspirin does not reduce the risk of vascular death, but provides a significant reduction in non-fatal stroke, myocardial infarction and non-vascular death. Our findings would support presenting the effect of aspirin therapy on individual outcomes rather than a composite including vascular death.
authors.affiliation: National University of Ireland, Galway, Ireland.
authors.forename: Emer
authors.initials: E
authors.lastname: McGrath
authors.forename: Aengus
authors.initials: A
authors.lastname: O'Conghaile
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Sean F
authors.initials: SF
authors.lastname: Dinneen
authors.forename: Colin
authors.initials: C
authors.lastname: Oczkowski
authors.forename: Martin J
authors.initials: MJ
authors.lastname: O'Donnell
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D017063:Outcome Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin