Aspirin plus clopidogrel versus aspirin mono-therapy for ischemic stroke: a meta-analysis

Objectives. Stroke is a common condition after a transient ischemic attack (TIA) or minor ischemic stroke (IS). Adding clopidogrel to aspirin may yield more beneficial outcomes than aspirin mono-therapy; meanwhile, the risk of bleeding in the acute phase remains poorly understood. Therefore, there is increasing emphasis on the risks and benefits of clopidogrel with aspirin compared with aspirin mono-therapy in an effort to treat TIA/IS. Design. We searched several electronic databases, including PubMed, Cochrane, and Embase, to identify eligible randomized controlled trials (RCTs) based on the index words comparing dual-antiplatelet therapy to aspirin mono-therapy for secondary stroke prevention updated to December, 2018. Results. A total of 11 RCTs met our inclusion criteria. The pooled analysis showed that clopidogrel plus aspirin was associated with a trend toward a reduction in recurrent IS (RR=0.72, 95%CI= 0.65-0.81, p<.001), but not the recurrent stroke rate (RR=0.81, 95% CI=0.63-1.03, p=.09) than aspirin mono-therapy. There were differences in bleeding episodes (RR=1.81, 95%CI=1.65-1.99, p<.001), moderate-severe major bleeding (RR=1.64, 95% CI=1.24-2.16, p=.0005), or mild bleeding (RR=2.25, 95%CI=1.54-3.31, p<.001) between the study groups. Meanwhile, no benefit of reducing the risk of intracranial hemorrhage with dual-antiplatelet therapy was found in TIA/IS patients (RR=1.44, 95% CI=0.95-2.19, p=.09). Conclusions. The addition of clopidogrel to aspirin for patients with TIA or IS appeared to significantly reduce the risk of IS recurrence with a possible increase in the risk of bleeding compared with aspirin alone.