Clinical outcomes stratified by CYP2C19 phenotypes in intracranial artery stenting patients with genotype-guided antiplatelet regimens: a real-world single-center retrospective cohort study

OBJECTIVES: Clinical trial evidence is scarce for optimal antiplatelet strategies in patients undergoing intracranial artery stenting with CYP2C19 loss‑of‑function alleles, especially regarding the efficacy‑safety balance. METHODS: This single‑center retrospective study enrolled patients receiving genotype‑guided antiplatelet regimens for intracranial stenting between January and December 2023, with 6‑month follow‑up. Clinical outcomes were compared across CYP2C19 phenotypes. RESULTS: Among 205 patients, 46.8% were normal metabolizers, 40.5% intermediate metabolizers, and 12.7% poor metabolizers. Aspirin-clopidogrel was prescribed for all normal metabolizers, 80.7% intermediate metabolizers, and 19.2% poor metabolizers. No intergroup differences were observed in risks of ischemic stroke/transient ischemic attack (TIA), cardiovascular events, intracerebral hemorrhage (ICH), or any bleeding (all P > 0.05). In intermediate metabolizers and poor metabolizer subgroups, ischemic stroke/TIA rates were 11.1% in the aspirin-clopidogrel group and 9.68% in the aspirin-ticagrelor group, with no significant difference compared to normal metabolizers (4.17%). ICH rates were 1.39% in the aspirin-clopidogrel group and 6.45% in the aspirin-ticagrelor group, showing no significant difference versus normal metabolizers (1.04%). Multivariate logistic analysis found the number of stents (odds ratio [OR] = 2.70; 95% confidence interval [CI] = 0.89-6.95; P = 0.043) was a risk factor for ischemic stroke/TIA. Ticagrelor-based dual antiplatelet therapy (DAPT; OR = 10.57; 95% CI = 1.00-111.7; P = 0.05) and baseline l ow-density lipoprotein cholesterol (LDL-C; OR = 7.22; 95% CI = 1.80-29.01; P = 0.005) were associated with ICH risk. CONCLUSION: Antiplatelet regimens were adjusted for a subset of intermediate metabolizers and poor metabolizers prior to stenting, and the 6-month clinical outcomes were comparable across normal metabolizers, intermediate metabolizers, and poor metabolizers. The stent number was associated with ischemic stroke/TIA risk; baseline LDL-C and ticagrelor-based DAPT with ICH risk. These exploratory findings need validation in adequately powered studies.