Dual antiplatelet therapy guided by CYP2C19 polymorphism after intracranial or extracranial stenting: A single-center...

To evaluate the efficacy and safety of three distinct dual antiplatelet therapy (DAPT) strategies following intracranial and extracranial neurovascular stenting. under the guidance of CYP2C19 genotyping.

In this single-center, retrospective cohort study, consecutive patients who underwent elective neurovascular stenting in the Department of Neurology, Second Affiliated Hospital of Xi'an Jiaotong University, from January 2020 to December 2024 and completed 90-day follow-up were retrospectively enrolled. All patients received DAPT for 90 days (starting 3 days before the procedure). In Part I, patients were stratified into a genotype-guided group (n = 938) and a conventional group (n = 218) according to whether CYP2C19 genotyping was performed. In the genotype-guided group, CYP2C19 rapid metabolizers received clopidogrel (75 mg qd) plus aspirin (100 mg qd), whereas intermediate or poor metabolizers received ticagrelor (90 mg bid) or cilostazol (100 mg bid) plus aspirin (100 mg qd). The conventional group received clopidogrel plus aspirin. The primary efficacy outcome was new ischemic stroke within 90 days. In Part II, genotype-guided patients were further classified into clopidogrel, ticagrelor, and cilostazol subgroups, all combined with aspirin. The primary efficacy endpoint remained 90-day ischemic stroke; the primary safety endpoint was moderate-to-severe bleeding within 90 days.

Of 1,270 included patients, 1,156 completed 90-day follow-up. Baseline characteristics were balanced between the genotype-guided and conventional groups (all P > 0.05). The 90-day ischemic stroke rate was significantly lower with genotype-guided therapy (3.73 % vs 6.88 %; P = 0.039). Within the genotype-guided cohort, baseline variables were balanced across clopidogrel (n = 386), ticagrelor (n = 330), and cilostazol (n = 222) subgroups (all P > 0.05). A significant difference in ischemic stroke rates was observed among the three DAPT regimens (P = 0.034), forming an efficacy gradient: clopidogrel in rapid metabolizers (2.33 %), ticagrelor (3.63 %), and cilostazol (5.96 %). Post-hoc analysis showed a higher risk with cilostazol versus clopidogrel (relative risk 2.55; P = 0.0097). The incidence of moderate-to-severe bleeding was similar low across all groups (clopidogrel 0.42 %, ticagrelor 0.61 %, cilostazol 0.33 %; P > 0.05), However, ticagrelor was associated with a significantly higher rate of any bleeding event (7.27 %) compared to both clopidogrel (2.33 %) and cilostazol (0.99 %). Multivariable analysis established the DAPT regimen as an independent predictor of ischemic stroke.

CYP2C19 genotype- DAPT significantly reduces the risk of ischemic stroke within 90 days after intracranial or extracranial stenting. For CYP2C19 loss-of-function allele carriers, ticagrelor plus aspirin offers a more effective antithrombotic effect compared to cilostazol plus aspirin, albeit with a higher risk of manageable bleeding events. An individualized strategy is recommended: ticagrelor should be prioritized for ischemic prevention in most patients, while cilostazol represents a safer alternative for those at very high bleeding risk.