Summary
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.
