Division of Cardiology, MedStar Washington Hospital Center, Washington, DC 20010, USA.
Am Heart J. 2013 Aug;166(2):266-72. doi: 10.1016/j.ahj.2013.04.008. Epub 2013 May 23.
On-treatment platelet reactivity to clopidogrel is variable and in part genetic dependent. In African American (AA) patients, the relation between on-treatment platelet reactivity to clopidogrel and the factors that influence this interaction is unknown. The present study aims to evaluate on-treatment platelet reactivity to clopidogrel in AA patients and its interaction to race and CYP2C19*2 loss of function mutation.
The study cohort included 289 consecutive patients presenting for percutaneous coronary intervention who were entered into a prospective observational registry. High on-treatment platelet reactivity (HTPR) was defined as P2Y12 reaction units (PRU) ≥208 with VerifyNow P2Y12 assay and >50% by vasodilator-stimulated phosphoprotein phosphorylation assay platelet reactivity index (VASP PRI) measured 6 to 24 hours postprocedure. CYP2C19*2 (rs4244285) genotype was analyzed by real-time polymerase chain reaction.
The prevalence of HTPR by both PRU (56% vs 35%, P = .003) and VASP PRI (67% vs 45%, P = .002) is more common in AAs compared with whites, respectively. African American patients had higher on-treatment mean PRU (207 ± 110 vs 160 ± 102, P = .002) and VASP PRI (49 ± 26 vs 38 ± 26, P = .004). African Americans also had a higher prevalence of CYP2C192 allele carrier status compared with whites (43% vs 29%, P = .04). African American race (P = .008) and CYP2C192 allele status (P = .02) independently had significant effects on PRU and VASP. Multivariable logistic regression analysis has shown that both CYP2C19*2 allele carrier status and AA race were independent correlates of HTPR for PRU ≥208.
African American patients undergoing percutaneous coronary intervention not only have a higher prevalence of HTPR to clopidogrel but also have higher CYP2C19*2 allele carrier status compared with whites. Careful selection of antiplatelet agents should be considered in an AA population at higher risk for ischemic complications.
氯吡格雷治疗中的血小板反应性存在个体差异，部分与遗传因素有关。在非裔美国人（AA）患者中，氯吡格雷治疗中的血小板反应性与影响这种相互作用的因素之间的关系尚不清楚。本研究旨在评估 AA 患者氯吡格雷治疗中的血小板反应性及其与种族和 CYP2C19*2 无功能突变的相互作用。
研究队列包括 289 例连续行经皮冠状动脉介入治疗的患者，他们被纳入前瞻性观察性登记研究。高血小板反应性（HTPR）定义为用 VerifyNow P2Y12 检测血小板反应单位（PRU）≥208 和用血管扩张刺激磷酸蛋白磷酸化检测血小板反应指数（VASP PRI）≥50%，检测时间为术后 6-24 小时。通过实时聚合酶链反应分析 CYP2C19*2（rs4244285）基因型。
通过 PRU（56%比 35%，P=0.003）和 VASP PRI（67%比 45%，P=0.002）检测到的 HTPR 在 AA 中比白人更常见。与白人相比，AA 患者的治疗中平均 PRU（207±110 比 160±102，P=0.002）和 VASP PRI（49±26 比 38±26，P=0.004）更高。与白人相比，AA 患者 CYP2C192 等位基因携带状态的发生率也更高（43%比 29%，P=0.04）。AA 种族（P=0.008）和 CYP2C192 等位基因状态（P=0.02）对 PRU 和 VASP 均有显著影响。多变量逻辑回归分析显示，CYP2C19*2 等位基因携带状态和 AA 种族均是 PRU≥208 的 HTPR 的独立相关因素。
行经皮冠状动脉介入治疗的 AA 患者不仅氯吡格雷治疗中的 HTPR 发生率较高，而且 CYP2C19*2 等位基因携带状态也较高。在缺血性并发症风险较高的 AA 人群中，应谨慎选择抗血小板药物。
