Among clopidogrel-treated patients after DES implantation, carrying a CYP2C19 loss-of-function allele was associated with an increased risk of cardiac death, MI, or stent thrombosis (HR 1.48; 95% CI 1.05-2.07).
Cohort (n=8,163)
Yes
Does the CYP2C19 loss-of-function allele increase the risk of a composite of cardiac death, MI, and stent thrombosis in clopidogrel-treated patients after DES implantation?
Carriage of the CYP2C19 loss-of-function allele is associated with higher ischemic risk in clopidogrel-treated patients after DES implantation, particularly in those with high clinical risk or acute coronary syndrome presentation.
Hazard Ratio: 1.48 (95% CI 1.05–2.07)
p-value: p=< 0.001
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‐P 2 A 2 RC 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 (HR adj : 1.68; 95% CI: 1.01–2.80; P = 0.047 and HR adj : 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‐P 2 A 2 RC (HR adj : 2.12; 95% CI: 1.11–4.03 and HR adj : 0.68; 95% CI: 0.34–1.36; P interaction = 0.017) and TRS 2°P scores (HR adj : 2.34; 95% CI: 1.07–5.12 and HR adj : 0.52; 95% CI: 0.22–1.17; P interaction = 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.
Park et al. (Sun,) conducted a cohort in Drug-eluting stent (DES) implantation (n=8,163). CYP2C19 loss-of-function (LoF) allele (intermediate or poor metabolizers) vs. Rapid or normal metabolizers (RMs/NMs) was evaluated on Composite of cardiac death, myocardial infarction, and stent thrombosis (HR 1.48, 95% CI 1.05-2.07, p=< 0.001). Among clopidogrel-treated patients after DES implantation, carrying a CYP2C19 loss-of-function allele was associated with an increased risk of cardiac death, MI, or stent thrombosis (HR 1.48; 95% CI 1.05-2.07).