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.