摘要

Genet Med 18 8, 833–841. Purpose: We evaluated the incremental prognostic value of combining the CYP2C19 poor metabolizer (PM) and ABCB1 3435 TT for adverse clinical outcomes over conventional risk factors in a percutaneous coronary intervention (PCI) cohort. Methods: We enrolled 2,188 patients. The primary end point was a composite of death from any cause, nonfatal myocardial infarction (MI), and stroke during 1-year follow-up. The population was stratified into the following four groups: CYP2C19 EM/IM+ ABCB1 3435 CC/CT, CYP2C19 EM/IM+ ABCB1 3435 TT, CYP2C19 PM+ ABCB1 3435 CC/CT, and CYP2C19 PM+ ABCB1 3435 TT. Results: A total of 87 (3.97%) primary end-point events occurred (64 deaths, 8 non-fatal MIs and 15 strokes). Multivariate Cox analysis indicated that CYP2C19 PM+ ABCB1 3435 TT status was a significant predictor of the primary end point (hazard ratio = 4.51, 95% confidence interval (CI) = 1.92–10.58). However, addition of combined genetic status to the clinical risk model did not improve the model discrimination (C-statistic = 0.786 (95% CI = 0.734–0.837) to 0.785 (95% CI = 0.733–0.838)) or risk reclassification (categorical net reclassification improvement (0.040, P = 0.32), integrated discrimination improvement (0.021, P = 0.026)). Conclusions: In a real-world East Asian PCI population taking clopidogrel, although the concurrent presence of CYP2C19 PM and ABCB1 TT is a strong independent predictor of adverse outcomes, the combined status of two at-risk variants does not have an incremental prognostic value beyond that of the conventional clinical risk factors.

译文

Genet Med 18 8，833-841。目的: 我们评估了在经皮冠状动脉介入治疗 (PCI) 队列中，结合 CYP2C19 低代谢 (PM) 和 ABCB1 3435 TT 对传统危险因素的不良临床结果的增量预后价值。方法: 我们招募了 2,188 名患者。主要终点是任何原因导致的死亡、非致死性心肌梗死 (MI) 和 1 年随访期间的中风的复合。人群被分为以下四组: CYP2C19 EM/IM ABCB1 3435 CC/CT，CYP2C19 EM/IM ABCB1 3435 TT，CYP2C19 PM ABCB1 3435 CC/CT, 和 CYP2C19 PM ABCB1 3435 TT。结果: 共发生 87 例 (3.97%) 主要终点事件 (64 例死亡，8 例非致命 MIs 和 15 例中风)。多变量 Cox 分析表明 CYP2C19 PM ABCB1 3435 TT 状态是主要终点的重要预测因子 (风险比 = 4.51，95% 置信区间 (CI) = 1.92-10.58)。然而，在临床风险模型中添加联合遗传状态并没有提高模型的区分度 (C-统计量 = 0.786 (95% CI = 0.734-0.837) 至 0.785 (95% CI = 0.733-0.838)) 或风险重新分类 (分类净重新分类改善 (0.040，P = 0.32)，综合区别改善 (0.021，P = 0.026))。结论: 在现实世界中，东亚人群服用氯吡格雷，尽管 CYP2C19 PM 和 ABCB1 TT 的同时存在是不良后果的强独立预测因子, 两种高危变异的联合状态除了常规临床风险因素外，没有增加预后价值。