Dörr Gesine, Schmidt Gunter, Gräfe Michael, Regitz-Zagrosek Vera, Fleck Eckart
Department of Medicine/Cardiology, Charité, Campus Virchow Klinikum, Humboldt Universität Berlin, Augustenburgerplatz 1, D-13353 Berlin, Germany.
J Cardiovasc Pharmacol. 2002 Apr;39(4):523-32. doi: 10.1097/00005344-200204000-00008.
This study aimed to compare the effects of clopidogrel, acetylsalicylic acid (ASA), and the combination of both substances on platelet aggregation and expression of platelet membrane glycoproteins in patients with chronic coronary artery disease. We investigated platelet activation by flow cytometry and by platelet aggregation and disaggregation in 60 patients randomly assigned to 3 treatment groups: ASA, clopidogrel, combination of clopidogrel and ASA, treated for 14 days. Adenosine diphosphate (ADP)-induced expression of P-selectin and of PAC-1 was significantly reduced after 2 wk of clopidogrel but not of ASA treatment. Treatment with clopidogrel reduced the ADP-induced platelet aggregation. The combination of clopidogrel and ASA did not increase the inhibition of platelet activation compared with clopidogrel alone. A significant increase in platelet disaggregation was observed with clopidogrel alone and was more pronounced with the combination of clopidogrel and ASA. ADP-induced platelet degranulation, activation of GPIIb/IIIa receptor, and aggregation in vivo are effectively inhibited by clopidogrel. The significantly increased disaggregation under clopidogrel and ASA suggests that the combined therapy may be superior to the monotherapy in patients with coronary artery disease and a high risk for vascular events.
本研究旨在比较氯吡格雷、阿司匹林（ASA）以及两者联合用药对慢性冠状动脉疾病患者血小板聚集和血小板膜糖蛋白表达的影响。我们通过流式细胞术以及血小板聚集和解聚试验，对随机分为3个治疗组（ASA组、氯吡格雷组、氯吡格雷与ASA联合组）的60例患者进行了为期14天的治疗，以研究血小板激活情况。氯吡格雷治疗2周后，二磷酸腺苷（ADP）诱导的P-选择素和PAC-1表达显著降低，而ASA治疗则未出现此现象。氯吡格雷治疗可降低ADP诱导的血小板聚集。与单用氯吡格雷相比，氯吡格雷与ASA联合用药并未增强对血小板激活的抑制作用。单用氯吡格雷可观察到血小板解聚显著增加，氯吡格雷与ASA联合用药时更为明显。氯吡格雷可有效抑制ADP诱导的血小板脱颗粒、糖蛋白IIb/IIIa受体激活及体内聚集。氯吡格雷与ASA联合用药时血小板解聚显著增加，提示联合治疗在冠状动脉疾病且血管事件风险高的患者中可能优于单药治疗。
