Dalby Miles, Montalescot Gilles, Bal dit Sollier Claire, Vicaut Eric, Soulat Thierry, Collet Jean Philippe, Choussat Rémi, Gallois Vanessa, Drobinski Gérard, Drouet Ludovic, Thomas Daniel
Institut de Cardiologie, Pitié-Salpétrière University Hospital, Paris, France.
J Am Coll Cardiol. 2004 Jan 21;43(2):162-8. doi: 10.1016/j.jacc.2003.08.033.
The present study hypothesis was that eptifibatide offered further antiplatelet efficacy above clopidogrel in non-ST-elevation myocardial infarction (NSTEMI) patients before an expeditive coronary intervention.
Although thienopyridines and glycoprotein (GP) IIb/IIIa antagonists are often co-prescribed in the context of NSTEMI, the antiplatelet interaction of these agents is poorly described and the superiority of GP IIb/IIIa antagonists above thienopyridine treatment alone is not clear.
Thirty-two NSTEMI patients treated with aspirin and enoxaparin were studied using flow cytometry to define parameters of platelet activation with a panel of agonists before clopidogrel, after clopidogrel, and during an eptifibatide infusion following the clopidogrel load.
After platelet activation with adenosine diphosphate, thrombin receptor-activating peptide, or U46-619, relative reductions in conformationally activated GP IIb/IIIa receptor expression (evaluated with PAC-1) of 48%, 43%, and 33%, respectively (all p < 0.0001), were seen with clopidogrel, but further 80%, 78%, and 72% (all p < 0.0001) reductions were seen with eptifibatide. With the same agonists, fibrinogen binding was significantly reduced after clopidogrel by 70%, 64%, and 81% (all p < 0.0001) and again further reduced with eptifibatide by 90%, 95%, and 69% (all p < 0.0001). The total number of GP IIb/IIIa receptors (measured as P2 expression) and P-selectin expression fell after clopidogrel, after ex vivo stimulation with the same agonists; however, both parameters increased slightly during the eptifibatide infusion.
The activated GP IIb/IIIa expression and fibrinogen binding findings indicate that eptifibatide provides significant potent antiplatelet activity above aspirin and clopidogrel, suggesting additive immediate protection in the treatment of NSTEMI. The P2 and P-selectin findings suggest the possibility of a partial agonist and/or pro-inflammatory effect.
本研究的假设是，在进行急诊冠状动脉介入治疗前，依替巴肽在非ST段抬高型心肌梗死（NSTEMI）患者中具有比氯吡格雷更强的抗血小板疗效。
尽管噻吩并吡啶类药物和糖蛋白（GP）IIb/IIIa拮抗剂常在NSTEMI治疗中联合使用，但这些药物的抗血小板相互作用描述甚少，且GP IIb/IIIa拮抗剂单独使用优于噻吩并吡啶类药物治疗的优势并不明确。
对32例接受阿司匹林和依诺肝素治疗的NSTEMI患者，在服用氯吡格雷前、服用氯吡格雷后以及氯吡格雷负荷量后输注依替巴肽期间，使用流式细胞术，用一组激动剂来确定血小板活化参数。
在用二磷酸腺苷、凝血酶受体激活肽或U46-619激活血小板后，氯吡格雷使构象活化的GP IIb/IIIa受体表达（用PAC-1评估）相对降低，分别为48%、43%和33%（均p<0.0001），而依替巴肽使该表达进一步降低80%、78%和72%（均p<0.0001）。使用相同激动剂时，氯吡格雷使纤维蛋白原结合显著降低70%、64%和81%（均p<0.0001），依替巴肽再次使纤维蛋白原结合进一步降低90%、95%和69%（均p<0.0001）。在用相同激动剂进行体外刺激后，氯吡格雷使GP IIb/IIIa受体总数（以P2表达量衡量）和P-选择素表达量下降；然而，在输注依替巴肽期间，这两个参数均略有增加。
活化的GP IIb/IIIa表达和纤维蛋白原结合的结果表明，依替巴肽在阿司匹林和氯吡格雷基础上提供了显著的强效抗血小板活性，提示在NSTEMI治疗中具有额外的即时保护作用。P2和P-选择素的结果提示了部分激动剂和/或促炎作用的可能性。
Zotero 插件