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

Abstract

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. Methods: 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 I 2 test. Results: 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], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I 2 =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], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I 2 =37%) but not within 21 days or clopidogrel. Conclusions: 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.