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P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack

Originally published 2021;52:2250–2257

    Background and purpose:

    We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack.


    Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I2 test.


    Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83], I2=0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I2=0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I2=0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I2=94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I2=0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I2=41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67], I2=0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I2=37%) but not within 21 days or clopidogrel.


    In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.


    *Z.-X. Li, Y. Xiong, and H.-Q. Gu contributed equally.

    This manuscript was sent to Emmanuel Touzé, Guest Editor, for review by expert referees, editorial decision, and final disposition.

    The Data Supplement is available with this article at

    For Sources of Funding and Disclosures, see page 2256.

    Correspondence to: Yongjun Wang, MD, China National Clinical Research Center for Neurological Diseases, Vascular Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. Email


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