Effectiveness of CYP2C19 Genotype-Guided Antiplatelet Therapy Following Neurovascular Endovascular Procedures: A...

CYP2C19 loss-of-function alleles are highly prevalent in Asian populations and may reduce the effectiveness of clopidogrel. This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with symptomatic severe intracranial atherosclerotic stenosis undergoing neurovascular endovascular treatment (EVT).

This prospective non-randomized controlled study enrolled 175 patients who underwent neurovascular intervention. Patients in the genotype-guided group (n=100) received individualized antiplatelet therapy according to CYP2C19 genotyping results, whereas patients in the conventional therapy group (n=75) received routine dual antiplatelet therapy with aspirin and clopidogrel. Safety events, 90-day neurological outcomes, and the cumulative incidence of ischemic events within one year were compared between groups.

The incidence of bleeding events did not differ significantly between the genotype-guided group and the conventional therapy group (1.0% vs 4.0%, P>0.05). At 90 days, a significantly higher proportion of patients achieved a favorable functional outcome (modified Rankin Scale score 0-1) in the genotype-guided group than in the conventional therapy group (84.0% vs 65.3%, P=0.004). At one year, the proportion of patients experiencing at least one ischemic event was significantly lower in the genotype-guided group than in the conventional therapy group (12.0% vs 26.7%, P=0.013). Multivariable Cox regression analysis demonstrated that patients in the conventional therapy group had a significantly higher risk of ischemic events during follow-up than those in the genotype-guided therapy group (HR: 2.723, 95% CI: 1.259-5.888, P = 0.011). Interaction analysis suggested that treatment effects differed according to device type, with a numerically greater benefit observed in the stent subgroup, although this finding should be considered exploratory.

CYP2C19 genotype-guided antiplatelet therapy following neurovascular EVT was associated with improved neurological outcomes and a lower incidence of ischemic events without increasing bleeding risk. However, because ticagrelor exposure differed between treatment groups, the independent contribution of pharmacogenetic testing requires further confirmation in larger randomized studies.