Benefits and Risks of Dual Versus Single Antiplatelet Therapy for Secondary Stroke Prevention: A Systematic Review for the 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack

Background: Dual antiplatelet therapy (DAPT) after ischemic stroke or transient ischemic attack may reduce recurrent stroke but also increase severe bleeding compared with single antiplatelet therapy (SAPT). The American Heart Association/American Stroke Association convened an evidence review committee to perform a systematic review and meta-analysis of the benefits and risks of DAPT compared with SAPT for secondary ischemic stroke prevention. Methods: The Medline, Embase, and Cochrane databases were searched on December 5, 2019, to identify phase III or IV randomized controlled trials (n >= 100) from December 1999 to December 2019. We calculated unadjusted relative risks (RRs) and performed meta-analyses of studies based on the duration of treatment (short [<= 90 days] versus long [>90 days]). Results: Three short-duration randomized controlled trials were identified that enrolled mostly patients with minor stroke or high risk transient ischemic attack. In these trials, DAPT, compared with SAPT, was associated with a lower 90-day risk of recurrent ischemic stroke (pooled RR, 0.68 [95% CI, 0.55-0.83], I (2)=37.1%). There was no significant increase in major bleeding with DAPT in short-duration trials (pooled RR, 1.88 [95% CI, 0.93-3.83], I (2)=8.9%). In 2 long-duration treatment randomized controlled trials (mean treatment duration, 18-40 months), DAPT was not associated with a significant reduction in recurrent ischemic stroke (pooled RR, 0.89 [95% CI, 0.79-1.02], I (2)=1.4%), but was associated with a higher risk of major bleeding (pooled RR, 2.42 [95% CI, 1.37-4.30], I (2)=75.5%). Conclusions: DAPT was more effective than SAPT for prevention of secondary ischemic stroke when initiated early after the onset of minor stroke/high-risk transient ischemic attack and treatment duration was <90 days. However, when the treatment duration was longer and initiated later after stroke or transient ischemic attack onset, DAPT was not more effective than SAPT for ischemic stroke prevention and it increased the risk of bleeding.