冠状动脉支架置入患者中对300毫克氯吡格雷负荷剂量反应低下者的识别。

Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting.

作者信息

Angiolillo Dominick J, Fernandez-Ortiz Antonio, Bernardo Esther, Ramírez Celia, Barrera-Ramirez Carlos, Sabaté Manel, Hernández Rosana, Moreno Raul, Escaned Javier, Alfonso Fernando, Bañuelos Camino, Costa Marco A, Bass Theodore A, Macaya Carlos

机构信息

Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA.

出版信息

Thromb Res. 2005;115(1-2):101-8. doi: 10.1016/j.thromres.2004.07.007.

DOI:10.1016/j.thromres.2004.07.007

PMID:15567460

Abstract

BACKGROUND

Although patients undergoing coronary stenting routinely receive dual antiplatelet treatment to reduce the risk of stent thrombosis, this undesired event still occurs. A suboptimal response to clopidogrel treatment (low responders) has been suggested to contribute to stent thrombosis. In the present study, platelet function profiles were assessed in patients undergoing coronary stenting receiving a standard 300-mg clopidogrel loading dose with the aim to identify low clopidogrel responders.

MATERIALS AND METHODS

Platelet aggregation was assessed by light transmittance aggregometry following 6 microM ADP stimuli in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front-loading. Patients having > or =40% inhibition of platelet aggregation 24 h after clopidogrel administration were defined as normal responders, whereas those having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed by whole blood flow cytometry following 2 microM ADP stimuli at the same time points. Platelet function profiles were compared between normal and low clopidogrel responders.

RESULTS

Twenty-seven patients (56%) were normal responders and 21 (44%) low responders. Baseline GP IIb/IIIa activation was higher in low responders (74.6+/-16.6% vs. 58.2+/-24.5%, p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front-loading in both groups, it remained increased among low responders at 24 h (58.6+/-21.3% vs. 40.2+/-28.7%, p=0.05) and during the overall study time course (p=0.02). There were no differences in P-selectin expression.

CONCLUSIONS

A considerable proportion of patients have an early suboptimal response to a 300-mg clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention may identify this group of patients suggesting the use of a more aggressive antithrombotic treatment in these individuals.

摘要

背景

尽管接受冠状动脉支架置入术的患者常规接受双联抗血小板治疗以降低支架血栓形成的风险，但这种不良事件仍会发生。有人提出对氯吡格雷治疗反应欠佳（低反应者）会导致支架血栓形成。在本研究中，对接受300毫克氯吡格雷标准负荷剂量的冠状动脉支架置入术患者的血小板功能谱进行了评估，目的是识别氯吡格雷低反应者。

材料和方法

在48例患者接受氯吡格雷负荷给药前、给药后10分钟、4小时和24小时，通过光透射聚集法在6微摩尔ADP刺激后评估血小板聚集。氯吡格雷给药后24小时血小板聚集抑制率≥40%的患者被定义为正常反应者，而抑制率<40%的患者为低反应者。在相同时间点，通过全血流式细胞术在2微摩尔ADP刺激后评估糖蛋白（GP）IIb/IIIa活化和P-选择素表达。比较正常和氯吡格雷低反应者之间的血小板功能谱。

结果

27例患者（56%）为正常反应者，21例（44%）为低反应者。低反应者的基线GP IIb/IIIa活化较高（74.6±16.6%对58.2±24.5%，p=0.03）。尽管两组在氯吡格雷负荷给药后GP IIb/IIIa活化均降低，但在24小时时低反应者中仍升高（58.6±21.3%对40.2±28.7%，p=0.05），且在整个研究时间过程中均升高（p=0.02）。P-选择素表达无差异。