AbstractAimOur study aimed to explore the effectiveness and safety of intravenous t‐PA compared with dual antiplatelet therapy (DAPT) and aspirin alone for minor stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤5 and large vessel occlusion (LVO).MethodsPatients with minor stroke harboring LVO within 4.5‐h time window were included from the Third China National Stroke Registry (CNSR‐III) between August 2015 and March 2018 in China. Clinical outcomes including modified Rankin scale (mRS) score, recurrent stroke, and all‐cause mortality at 90 days and 36‐h symptomatic intracerebral hemorrhage (sICH) were collected. Multivariable logistic regression models and propensity score matching analyses were used to determine the association between treatment groups and clinical outcomes.ResultsA total of 1401 minor stroke patients with LVO were included. Overall 251 patients (17.9%) received intravenous t‐PA, 722 patients (51.5%) received DAPT, and 428 patients (30.5%) received aspirin alone. The intravenous t‐PA was associated with greater proportions of mRS 0–1 (aspirin versus t‐PA: adjusted odds ratio [aOR], 0.50; 95% confidence interval [CI], 0.32 to 0.80;p= 0.004; DAPT versus t‐PA: aOR, 0.76; 95% CI, 0.49 to 1.19;p= 0.23). Using propensity score matching analyses, the results were similar. There was no difference in 90‐day recurrent stroke among the groups. The rates of all‐cause mortality in intravenous t‐PA, DAPT, and aspirin groups were 0%, 0.55%, 2.34%, respectively. No patient developed sICH within 36 h of intravenous t‐PA.ConclusionIn patients with minor stroke harboring LVO within 4.5‐h time window, intravenous t‐PA was associated with higher odds for the excellent functional outcome, as compared with the aspirin alone. Further randomized controlled trials are warranted.