在氯吡格雷抵抗患者中，根据 ABCB1 变异等位基因携带患者的血小板反应性监测结果调整氯吡格雷负荷剂量。
Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance.
机构信息
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
出版信息
Eur J Intern Med. 2012 Jan;23(1):48-53. doi: 10.1016/j.ejim.2011.07.016. Epub 2011 Sep 3.
OBJECTIVES
The aim of the present study was to investigate the impact of a adjusted clopidogrel loading dose (LD) according to platelet reactivity index in carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention (PCI).
METHODS
All patients met the inclusion criteria were recruited in the present study. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was determined by a cut-off value of >50%. The genetic polymorphism of ABCB1 was determined by allele-specific polymerase chain reaction (PCR). In patients carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 300-mg LDs to obtain a VASP index<50%. The rate of major adverse cardiovascular events (MACE) and major or minor bleeding in one month were recorded.
RESULTS
536 patients were included in the present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild allele (65.5±13.8% vs. 47.6±21.8%; p<0.001). Of the 172 ABCB1 mutant allele carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (66.9±12.8% vs.50.2±18.3%; <0.001). Finally, dose adjustment according to platelet reactivity monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele carriers exhibiting HTPR to reach a VASP index<50%. The rate of MACE and major or minor bleeding in one-month follow-up between the wild allele carriers and the mutant allele carriers didn't differentiate significantly.
CONCLUSIONS
Increased and adjusted clopidogrel loading dose according to platelet reactivity monitoring attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.
目的
本研究旨在探讨经皮冠状动脉介入治疗（PCI）中载有 ABCB1 突变等位基因的患者，根据血小板反应指数调整氯吡格雷负荷剂量（LD）对其的影响。
方法
本研究纳入了所有符合入组标准的患者。使用血管扩张刺激磷蛋白（VASP）指数测量血小板反应性。高治疗血小板反应性（HTPR）通过>50%的截断值确定。ABCB1 的遗传多态性通过等位基因特异性聚合酶链反应（PCR）确定。在接受氯吡格雷首次 300mg LD 后携带 ABCB1 且 HTPR 的患者中，通过使用多达 3 次额外的 300mg LD 来调整剂量，以获得 VASP 指数<50%。记录一个月内主要不良心血管事件（MACE）和主要或次要出血的发生率。
结果
本研究共纳入 536 例患者。172 例（32%）患者携带 ABCB1 突变等位基因（11 例纯合子[2%]和 161 例杂合子[30%]）。这些患者的 VASP 指数明显高于野生等位基因纯合子患者（65.5±13.8%比 47.6±21.8%；p<0.001）。在 172 例携带 ABCB1 突变等位基因的患者中，有 130 例被认为存在 HTPR。在接受第二次氯吡格雷 LD 后，这些患者的 VASP 指数明显降低（66.9±12.8%比 50.2±18.3%；<0.001）。最后，根据血小板反应监测调整剂量使 88%的 ABCB1 突变等位基因携带者和 91%的野生等位基因携带者达到 VASP 指数<50%。在一个月的随访中，野生等位基因携带者和突变等位基因携带者之间的 MACE 和主要或次要出血发生率没有显著差异。
结论
根据血小板反应性监测增加和调整氯吡格雷负荷剂量可减弱载有 ABCB1 突变等位基因患者的氯吡格雷抵抗。
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