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. Study Selection: All randomised controlled trials comparing aspirin with placebo/control in patients following ischaemic stroke or transient ischaemic attack, beyond the acute period (2 weeks). Data Analysis: 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.