Prognostic Implication of CYP2C19 Genotype According to Clinical Risk Stratification After Drug‐Eluting Stent Implantation

The impact of CYP2C19 genotype in relation to clinical risk is unclear during clopidogrel treatment following drug‐eluting stent (DES) implantation. This study aimed to evaluate the prognostic significance of CYP2C19 genotypes based on clinical risk stratification in DES‐treated patients. From the nationwide multicenter PTRG‐DES (Platelet function and genoType‐Related long‐term progGosis in DES‐treated patients) consortium, patients were classified according to the presence of CYP2C19 loss‐of‐function (LoF) allele: rapid or normal metabolizers (RMs/NMs) vs. intermediate or poor metabolizers (IMs/PMs), and clinical risk was stratified using the CHADS‐P2A2RC and TRS 2°P scores. The primary endpoint (1°EP) was a composite of cardiac death, myocardial infarction, and stent thrombosis during a 3‐year follow‐up. Among clopidogrel‐treated patients with CYP2C19 genotyping (n = 8,163), IMs/PMs (62.1%) demonstrated an increased risk of 1°EP compared with RMs/NMs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.05–2.07; Log‐rank P < 0.001), Most notable in those with high CHADS‐P2A2RC (≥ 4) and TRS 2°P (≥ 3) scores (HRadj: 1.68; 95% CI: 1.01–2.80; P = 0.047 and HRadj: 1.63; 95% CI: 1.05–2.54; P = 0.029, respectively). In patients with low scores, there was no difference in 1°EP between IMs/PMs vs. RMs/NMs; however, an interaction was observed between acute and chronic coronary syndromes for both low CHADS‐P2A2RC (HRadj: 2.12; 95% CI: 1.11–4.03 and HRadj: 0.68; 95% CI: 0.34–1.36; Pinteraction = 0.017) and TRS 2°P scores (HRadj: 2.34; 95% CI: 1.07–5.12 and HRadj: 0.52; 95% CI: 0.22–1.17; Pinteraction = 0.008). Among clopidogrel‐treated patients, the carriage of the CYP2C19 LoF allele was associated with higher ischemic risk, particularly in those with high clinical risk or an acute coronary syndrome presentation.