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

CYP2C19

CYP2C19 phenotype governing clopidogrel bioactivation and the choice of dual antiplatelet regimen

Single-centre retrospective cohort of 205 patients who underwent intracranial artery stenting in 2023 under genotype-guided dual antiplatelet therapy, with six-month follow-up. CYP2C19 phenotypes were distributed as 46.8% normal metabolizers, 40.5% intermediate and 12.7% poor, with aspirin-clopidogrel prescribed to all normal metabolizers, 80.7% of intermediate and 19.2% of poor metabolizers. No between-group difference was found for ischaemic stroke or TIA, cardiovascular events, intracerebral haemorrhage or any bleeding (all P > 0.05). Among intermediate and poor metabolizers, ischaemic stroke/TIA rates were 11.1% on aspirin-clopidogrel and 9.68% on aspirin-ticagrelor, not significantly different from normal metabolizers (4.17%). On multivariable analysis, the number of stents was associated with ischaemic risk (OR = 2.70; 95% CI 0.89-6.95; P = 0.043), while ticagrelor-based dual therapy (OR = 10.57; 95% CI 1.00-111.7; P = 0.05) and baseline LDL cholesterol (OR = 7.22; 95% CI 1.80-29.01; P = 0.005) were associated with intracerebral haemorrhage.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value of this series is not in demonstrating a genotype effect but in showing that, after treatment adaptation, CYP2C19 intermediate and poor metabolizers match normal metabolizers on six-month events: that is the expected result of a genotype-guided strategy that works, not evidence that genotype does not matter. Interpretation must remain cautious, this is a single-centre cohort of 205 patients with no ungenotyped control arm and very wide confidence intervals, the ticagrelor estimate spanning 1.00 to 111.7. The most practically interesting secondary signal lies elsewhere: the excess intracerebral haemorrhage risk with ticagrelor-based dual therapy, a reminder that switching a poor metabolizer away from clopidogrel is not a decision without a trade-off.

Analysis by Dr Thibaut Benquey