Clinical Impact of Genetics on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention Using DrugEluting Stent

초록

Background Although CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether genotype-guided strategy can be generally adopted in routine practice remains unclear. Methods Of 13,160 patients from the nationwide multicenter PTRG-DES registry, patients who underwent CYP2C19 genotyping were selected. Patients were classified according to predicted CYP2C 19 phenotypes: extensive metabolizer (EM) vs intermediate (IM) or poor metabolizer (PM). Primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5-year after index procedure. Results Of 8,163 patients who underwent CYP2C19 genotyping, there were 3,098 (37.9%) in the EM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. Mean age of the study population was 64.2 ± 10.8 years, 65.1% were male, and 56.7% were presented with acute coronary syndrome. P2Y12 reaction unit level was significantly different among the 3 groups (EM 194.6 ± 79.5 vs IM 225.0 ± 73.2 vs PM 252.2 ± 74.9; P < 0.001). IM or PM group was associated with an increased risk of 5-year primary outcome compared with EM group (HRadj 1.42, 95% CI 1.01-1.98; P = 0.041). Unguided de-escalation to clopidogrel monotherapy for IM or PM group was associated with an increased risk of primary outcome at 5 years, compared with EM group without clopidogrel monotherapy (HRadj 2.10, 95% CI 1.35-3.25; P < 0.001). Conclusion In patients with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping can stratify patients who are likely to have an increased risk of long-term cardiac death, myocardial infarction, and stent thrombosis.