Herbert J M, Dol F, Bernat A, Falotico R, Lalé A, Savi P
Sanofi Recherche, Haemobiology Research Department, Toulouse, France.
Thromb Haemost. 1998 Sep;80(3):512-8.
It is unknown whether the addition of aspirin might increase both the efficacy and the potency of clopidogrel, a potent and selective ADP blocker. For that purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to rabbits alone or in combination with aspirin (0.1-10 mg/kg, p.o.) was determined in several experimental models. A potent synergistic effect of the clopidogrel/aspirin association was demonstrated with regard to collagen-induced platelet aggregation measured ex vivo. Similarly, aspirin potentiated the antithrombotic activity of clopidogrel measured with regard to experimental thrombosis induced by a silk thread or on stents placed in an arteriovenous shunt, thrombus formation following electrical stimulation of the rabbit carotid artery and with regard to 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt or on the subendothelium following air drying injury of the rabbit carotid artery. A similar potentiating effect of aspirin was obtained with regard to myointimal proliferation (restenosis) in the femoral arteries of atherosclerotic rabbits which occurred as a consequence of stent placement. The clopidogrel/aspirin combination showed only additive-type effects on bleeding time prolongation induced by ear transection in the rabbit, therefore showing that combined inhibition of cyclooxygenase and ADP's effects provide a marked enhanced antithrombotic efficacy. Such a combination may provide substantial protection against platelet aggregation leading to thrombotic occlusion at sites of endothelial injuries and coronary artery stenosis in humans.
尚不清楚添加阿司匹林是否会增强氯吡格雷（一种强效且选择性的 ADP 阻滞剂）的疗效和效力。为此，在多个实验模型中测定了单独口服给予兔子氯吡格雷（1 - 20 mg/kg，口服）或与阿司匹林（0.1 - 10 mg/kg，口服）联合使用时的疗效。在体外测量的胶原诱导的血小板聚集方面，证明了氯吡格雷/阿司匹林组合具有强效协同作用。同样，在丝线诱导的实验性血栓形成、置于动静脉分流中的支架上、兔颈动脉电刺激后的血栓形成以及在动静脉分流中植入的支架上或兔颈动脉空气干燥损伤后的内皮下 111In 标记血小板沉积方面，阿司匹林增强了氯吡格雷的抗血栓活性。在因支架置入导致的动脉粥样硬化兔股动脉内膜增生（再狭窄）方面，也获得了阿司匹林类似的增强作用。氯吡格雷/阿司匹林组合在兔耳横断诱导的出血时间延长方面仅表现出相加作用，因此表明环氧合酶和 ADP 作用的联合抑制可显著增强抗血栓疗效。这种组合可能为人类在内皮损伤部位和冠状动脉狭窄处预防血小板聚集导致的血栓闭塞提供实质性保护。
