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

초록

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&#xb0;P scores. The primary endpoint (1&#xb0;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&#x2009;=&#x2009;8,163), IMs/PMs (62.1%) demonstrated an increased risk of 1&#xb0;EP compared with RMs/NMs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.05-2.07; Log-rank P&#x2009;<&#x2009;0.001), Most notable in those with high CHADS-P2A2RC (&#x2265;&#x2009;4) and TRS 2&#xb0;P (&#x2265;&#x2009;3) scores (HRadj: 1.68; 95% CI: 1.01-2.80; P&#x2009;=&#x2009;0.047 and HRadj: 1.63; 95% CI: 1.05-2.54; P&#x2009;=&#x2009;0.029, respectively). In patients with low scores, there was no difference in 1&#xb0;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&#x2009;=&#x2009;0.017) and TRS 2&#xb0;P scores (HRadj: 2.34; 95% CI: 1.07-5.12 and HRadj: 0.52; 95% CI: 0.22-1.17; Pinteraction&#x2009;=&#x2009;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. © 2025 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

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