[Efficacy and mechanism of loading dose clopidogrel in patients with transient ischemic attack and minor stroke]

Objective: To assess outcome, safety and possible mechanism of loading dose clopidogrel in patients with transient ischemic attack (TIA) and minor stroke. Methods: We reviewed patients with confirmed TIA and minor stroke admitted between July 2016 and December 2017 into the First Affiliated Hospital of Soochow University. Loss-of-function allele carriers of CYP2C19 were included and randomly divided into loading dose group (first dose of 300 mg clopidogrel) and standard dose group (first dose of 75 mg clopidogrel), 100 mg aspirin was gave at the same time, followed by aspirin 100 mg/d plus clopidogrel 75 mg/d maintaining for 20 days. Platelet aggregation (maximum aggregation ratio, MAR) induced by Adenosine diphosphate (ADP) was examined before and 3 days after administration. The National Institutes of Health Stroke Scale (NIHSS) score method was employed to assess the NIHSS scores before and after treatment in each group of patients; the modified Rankin Scale (mRS) was used to assess the 3-month functional outcome. Results: There was no significant difference in baseline data between the two groups (P>0.05).The proportion of early neurological function improvement in the two groups was 75.0% and 54.8%, and the difference was statistically significant (χ(2)=4.498, P=0.034). The 3-month prognosis was 79.5% and 61.3%, and the difference was statistically significant (χ(2)=4.000, P=0.045). Adverse events: 1 case in the loading dose group, 1 case in the standard dose group, the difference was not statistically significant (2.3% vs 1.6%, χ(2)=0.061, P=0.806). After 3 days of antiplatelet therapy, the MAR of the loading dose group decreased (11%±8%), and the MAR of the standard dose group decreased (9%±4%), the difference was statistically significant (P=0.013).In the loading dose group, there were 32 (72.7%)CYP2C19*2 carriers and 42 (95.5%)CYP2C19*2+*3 carriers; early neurological function improvement in 33 cases, accounting for 93.8% and 76.2%, respectively, and the difference was statistically significant (χ(2)=4.122, P=0.042). There were 35 patients with good prognosis in 3 months, accounting for 96.9% and 81.0%, respectively. The difference was statistically significant (χ(2)=4.310, P=0.038); MAR of CYP2C19*2 carrier was decreased (15%±5%), and MAR of CYP2C19*2+*3 carrier was decreased (12%±8%). The difference was statistically significant (P=0.039). Conclusions: Loading dose clopidogrel can improve the clinical prognosis of minor stroke/TIA without increasing the risk of bleeding. Loading dose clopidogrel may improve the prognosis of minor stroke/TIA by decreasing MAR of CYP2C19*2 carriers.