Morishima Yoshiyuki, Honda Yuko, Kamisato Chikako
Medical Science Department, Daiichi Sankyo Co., Ltd., Tokyo,
End-Organ Disease Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Pharmacology. 2019;103(1-2):17-22. doi: 10.1159/000494059. Epub 2018 Oct 19.
BACKGROUND/AIMS: Stent thrombosis is a serious complication after percutaneous coronary intervention and femoropopliteal endovascular intervention. The aim of this study was to determine the antithrombotic effects of a direct factor Xa inhibitor edoxaban alone or in combination with antiplatelet agents in a rat model of stent thrombosis.
Stainless steel stents (4 stents per rat) were placed in an extracorporeal arteriovenous shunt. The shunt was inserted into the carotid artery and the jugular vein in each rat to circulate blood. Stent thrombosis was induced by exposing the stents to arterial blood for 30 min. Protein content of the thrombus was measured. Edoxaban and antiplatelet agents (aspirin, clopidogrel, and ticagrelor) were orally administered before the thrombus induction.
Edoxaban (0.3-3 mg/kg), clopidogrel (1-10 mg/kg), aspirin (10-100 mg/kg), and ticagrelor (0.3-3 mg/kg) exerted significant and dose-dependent antithrombotic effects in a rat stent thrombosis model. The effect of edoxaban was comparable to that of antiplatelet agents. The combination of submaximal doses of edoxaban and clopidogrel or aspirin significantly potentiated the antithrombotic effects compared with antiplatelet agents alone.
These results suggest that edoxaban alone and in combination with clopidogrel or aspirin are promising antithrombotic therapies for the prevention of stent thrombosis.
背景/目的：支架内血栓形成是经皮冠状动脉介入治疗和股腘动脉血管腔内介入治疗后的一种严重并发症。本研究的目的是在大鼠支架内血栓形成模型中确定直接Xa因子抑制剂依度沙班单独或与抗血小板药物联合使用的抗血栓作用。
将不锈钢支架（每只大鼠4个支架）置于体外动静脉分流管中。将分流管插入每只大鼠的颈动脉和颈静脉以实现血液循环。通过使支架暴露于动脉血30分钟诱导支架内血栓形成。测量血栓的蛋白质含量。在诱导血栓形成前口服依度沙班和抗血小板药物（阿司匹林、氯吡格雷和替格瑞洛）。
依度沙班（0.3 - 3毫克/千克）、氯吡格雷（1 - 10毫克/千克）、阿司匹林（10 - 100毫克/千克）和替格瑞洛（0.3 - 3毫克/千克）在大鼠支架内血栓形成模型中发挥了显著的剂量依赖性抗血栓作用。依度沙班的作用与抗血小板药物相当。与单独使用抗血小板药物相比，次最大剂量的依度沙班与氯吡格雷或阿司匹林联合使用显著增强了抗血栓作用。
这些结果表明，依度沙班单独使用以及与氯吡格雷或阿司匹林联合使用是预防支架内血栓形成的有前景的抗血栓治疗方法。
