Guided P2Y12 inhibitor selection after rapid CYP2C19 genotyping in patients undergoing percutaneous coronary intervention

Dual antiplatelet therapy remains the standard treatment following percutaneous coronary intervention (PCI). While prasugrel and ticagrelor offer consistent antiplatelet effects, they increase bleeding risk compared with clopidogrel, which requires CYP2C19 bioactivation.

This study aimed to evaluate the impact of rapid CYP2C19 genotyping at the time of PCI on P2Y₁₂ inhibitor selection and clinical outcomes in real-world patients.

A total of 974 patients who underwent PCI and rapid CYP2C19 genotyping and received P2Y₁₂ inhibitor treatment were included. P2Y₁₂ inhibitor selection, P2Y₁₂ inhibitor switching, major atherothrombotic events (MAE; a composite of all-cause death, myocardial infarction, ischaemic stroke, stent thrombosis, or unstable angina requiring revascularisation), and bleeding events were assessed throughout the first year post-PCI. Time-varying Cox regression analysis was performed to assess event risk in patients treated with clopidogrel (reference) versus prasugrel/ticagrelor after stratifying by loss-of-function (LOF) status and adjusting for stratum-specific confounders.

Clopidogrel was prescribed more frequently at discharge among CYP2C19 non-LOF versus LOF carriers (43% [296/691] vs 31% [87/283]; p<0.001). The median duration of follow-up was 359 days (interquartile range [IQR] 190-362 days). Among LOF allele carriers de-escalating to clopidogrel, the median de-escalation time was 180 days (IQR 92-354 days). MAE were not significantly different between P2Y₁₂ inhibitor regimens after stratifying by LOF status (LOF-prasugrel/ticagrelor [n=147] vs LOF-clopidogrel [n=136]: adjusted hazard ratio [HR] 0.87 [95% confidence interval [CI]: 0.36-2.10]; non-LOF-prasugrel/ticagrelor [n=272] vs non-LOF-clopidogrel [n=419]: adjusted HR 1.26, 95% CI: 0.67-2.36). No significant differences in Bleeding Academic Research Consortium bleeding events were observed.

This real-world study shows that, among LOF carriers managed with rapid CYP2C19 genotyping and delayed de-escalation, ischaemic and bleeding event rates were not significantly different between those taking clopidogrel versus those taking prasugrel/ticagrelor, though findings should be interpreted cautiously.