Sex Differences in Prognostic Implications of CYP2C19 Genotype After Drug‐Eluting Stent Implantation

초록

Background Dual‐antiplatelet therapy is standard after percutaneous coronary intervention, but clopidogrel responsiveness varies with CYP2C19 loss‐of‐function alleles. Whether the genotype conveys different prognostic significance between sexes is uncertain. Methods We analyzed 4630 East‐Asian patients with acute coronary syndrome in the PTRG‐DES (Platelet Function– and Genotype‐Related Long‐Term Prognosis in Drug‐Eluting Stent–Treated Patients With Coronary Artery Disease) consortium with available CYP2C19 genotyping. Patients were classified as rapid/normal metabolizers versus intermediate/poor metabolizers. The primary end point was cardiac death, myocardial infarction, or definite stent thrombosis within 5 years. Results Among 4630 patients with acute coronary syndrome, 1708 (36.9%) were women. The prevalence of intermediate/poor metabolizer phenotypes was similar in women (61.8%) and men (62.5%). After multivariable adjustment for clinical, laboratory, and procedural confounders, intermediate/poor metabolizer carriers had a significantly higher risk of the 5‐year primary outcome in men compared with rapid/normal metabolizer carriers (adjusted hazard ratio [HR], 3.27 [95% CI, 1.58–6.74]; P=0.001). In contrast, no significant association was observed in women (adjusted HR, 1.21 [95% CI, 0.58–2.52]; P = 0.615). Intermediate/poor metabolizer status was also associated with a higher risk of 5‐year cardiac death in men only (adjusted HR, 7.01 [95% CI, 2.01–24.48]; P=0.002). Significant interactions between sex and CYP2C19 metabolizer status were observed for both the primary outcome (P for interaction=0.034) and cardiac death (P for interaction=0.049). Conclusions CYP2C19 loss‐of‐function allele status was a significant predictor of long‐term adverse cardiovascular outcomes in men but not in women, suggesting a sex‐specific prognostic difference in patients with acute coronary syndrome undergoing percutaneous coronary intervention. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028.

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