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Clopidogrel plus aspirin reduces subsequent strokes with minimal increased bleeding

This systematic review and meta-analysis of randomized controlled trials (RCTs) determined the effectiveness and safety of dual antiplatelet therapy (DAPT) with clopidogrel and aspirin comparedwith either of them alone when used for secondary prevention of a stroke or transient ischemic attack (TIA). Trials were included if they were RCTs, had treatment onset within three days of an acute minor ischemic stroke or high-risk TIA, and compared DAPT to a single antiplatelet. Outcomes included all nonfatal recurrent stroke, all-cause mortality, nonfatal moderate, and major extracranial bleeding, among others. Three trials that contained 10,447 patients were included in the analysis. Compared to aspirin monotherapy, DAPT reduced the risk of nonfatal recurrent stroke (relative risk [RR] 0.70; 95% CI, 0.61–0.80; absolute risk reduction 1.9%; number needed to treat553). There was no impact on all-cause mortality (RR 1.27; 95% CI, 0.73–2.23) or recurrent TIA (RR 0.90; 95% CI, 0.71–1.14). Additionally, there was no increase in moderate to severe extracranial bleeding, although there was a significant increase in mild or minor extracranial bleeding events (RR 2.22; 95% CI, 1.60–3.08; number needed to harm5143). Heterogeneity between the included trials was low. Most recurrent strokes occurred within 10 days of randomization, so any additional benefit beyond 21 days is unlikely. Bottom line: For patients presenting with minor ischemic stroke or TIA, administering 10 to 21 days of DAPT with clopidogrel and aspirin is recommended rather than either of them alone to reduce the risk of subsequent strokes. This study affirms guideline-based recommendations of using DAPT for 21 days after a TIA or stroke, followed by a single antiplatelet agent indefinitely.