Four trials were included with 48,855 patients. Trial size ranged from 2,736 to 20,332. Two trials assessed clopidogrel, one modified-release dipyridamole alone and three modified-release dipyridamole combined with aspirin. All trials were judged to be of good quality; one trial was open-label.
The CAPRIE trial found that clopidogrel was more effective than aspirin at preventing first vascular events (RRR 8.7, 95% CI 0.3 to 16.5), but found no significant results for any other outcomes.
The ESPS-2 trial found that modified-release dipyridamole with aspirin was more effective than aspirin alone (RR 0.76, 95% CI 0.63 to 0.93) and modified-release dipyridamole alone (RR 0.75, 95% CI 0.61 to 0.91) at preventing stroke. For some secondary outcomes, modified-release dipyridamole alone was no different to aspirin alone.
The ESPRIT trial found that modified-release dipyridamole with aspirin was more effective than aspirin alone at preventing first vascular events (HR 0.80, 95% CI 0.66 to 0.98) and composite outcomes where this was a component.
The PRoFESS trial found no significant difference between clopidogrel and modified-release dipyridamole with aspirin for preventing recurrent stroke, but found a significant benefit of modified-release dipyridamole with aspirin for preventing new or worsening congestive heart failure, and a benefit of clopidogrel for incidence of intercranial haemorrhage. Analysis of individual-level data found that clopidogrel reduced the risk of vascular events in people with multivascular disease (RRR 14.9, 95% CI 0.3 to 27.3).
In patients with prior stroke/transient ischaemic attack, the mixed-treatment comparison models found no evidence of differences between any of the treatments for the prevention of first ischaemic stroke, myocardial infarction, vascular death or all-cause mortality. There was evidence that clopidogrel was more effective than aspirin at preventing recurrent stoke (RR 0.752, 95% CI 0.60 to 0.92). Modified-release dipyridamole with aspirin was similarly also more effective than aspirin alone (RR 0.764, 95% CI 0.62 to 0.92). Clopidogrel reduced the risk of major bleeding compared with aspirin (RR 0.596, 95% CI 0.36 to 0.89). No mixed-treatment analysis was performed in patients with myocardial infarction or established peripheral artery disease.