Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Division of Cardiology, Department of Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA.
J Am Coll Cardiol. 2024 Apr 16;83(15):1370-1381. doi: 10.1016/j.jacc.2024.02.015.
An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear.
The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI).
A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y inhibitor treatment were included. The primary outcome was major atherothrombotic events (MAE) within 1 year after PCI. Cox regression was performed to assess event risk in clopidogrel-treated (reference) vs alternatively treated patients, with stabilized inverse probability weights derived from exposure propensity scores after stratifying by ABCD-GENE score and further by CYP2C19 loss-of-function (LOF) genotype.
Among patients with scores <10 (n = 3,200), MAE was not different with alternative therapy vs clopidogrel (weighted HR: 0.89; 95% CI: 0.65-1.22; P = 0.475). The risk for MAE also did not significantly differ by treatment among patients with scores ≥10 (n = 1,135; weighted HR: 0.75; 95% CI: 0.51-1.11; P = 0.155). Among CYP2C19 LOF allele carriers, MAE risk appeared lower with alternative therapy in both the group with scores <10 (weighted HR: 0.50; 95% CI: 0.25-1.01; P = 0.052) and the group with scores ≥10 (weighted HR: 0.48; 95% CI: 0.29-0.80; P = 0.004), while there was no difference in the group with scores <10 and no LOF alleles (weighted HR: 1.03; 95% CI: 0.70-1.51; P = 0.885).
These data support the use of alternative therapy over clopidogrel in CYP2C19 LOF allele carriers after PCI, regardless of ABCD-GENE score, while clopidogrel is as effective as alternative therapy in non-LOF patients with scores <10.
ABCD-GENE（年龄、体重指数、慢性肾脏病、糖尿病和 CYP2C19 基因变异）评分≥10 预测氯吡格雷疗效降低，但与替代治疗反应的相关性仍不清楚。
本研究旨在评估 ABCD-GENE 评分与经皮冠状动脉介入治疗（PCI）后氯吡格雷与替代 P2Y 抑制剂（普拉格雷或替格瑞洛）治疗的有效性之间的关系。
共纳入 4335 例接受 PCI、CYP2C19 基因分型和 P2Y 抑制剂治疗的患者。主要终点是 PCI 后 1 年内主要动脉血栓栓塞事件（MAE）。采用 Cox 回归评估氯吡格雷治疗（参考）与替代治疗患者的事件风险，使用来自暴露倾向评分的稳定逆概率权重进行分层，分为 ABCD-GENE 评分和进一步分为 CYP2C19 功能丧失（LOF）基因型。
在评分<10 的患者中（n=3200），替代治疗与氯吡格雷治疗的 MAE 无差异（加权 HR：0.89；95%CI：0.65-1.22；P=0.475）。在评分≥10 的患者中（n=1135），治疗之间的 MAE 风险也没有显著差异（加权 HR：0.75；95%CI：0.51-1.11；P=0.155）。在 CYP2C19 LOF 等位基因携带者中，替代治疗在评分<10 的患者中（加权 HR：0.50；95%CI：0.25-1.01；P=0.052）和评分≥10 的患者中（加权 HR：0.48；95%CI：0.29-0.80；P=0.004）的 MAE 风险似乎较低，而在评分<10 且无 LOF 等位基因的患者中（加权 HR：1.03；95%CI：0.70-1.51；P=0.885）则无差异。
这些数据支持在 PCI 后，无论 ABCD-GENE 评分如何，CYP2C19 LOF 等位基因携带者均使用替代治疗而非氯吡格雷，而在评分<10 的非 LOF 患者中，氯吡格雷与替代治疗同样有效。
