INHIBITORY EFFECT OF CLOPIDOGREL ON PLATELET-ADHESION AND INTIMAL PROLIFERATION AFTER ARTERIAL INJURY IN RABBITS

The possible activity of ticlopidine and its analogue clopidogrel in e arly atherogenesis was investigated. Incubation of rabbit platelets wi th the extracellular matrix produced by endothelial cells in culture i nduced massive platelet adherence in vitro. This phenomenon was strong ly reduced when platelets were isolated from rabbits that had been tre ated with a single dose of clopidogrel (10 mg/kg PO) or three doses of ticlopidine (each 200 mg/kg PO) (94% and 56% inhibition of platelet a dhesion, respectively). Three doses of aspirin (each 200 mg/kg PO) wer e ineffective. Air-drying injury of the rabbit carotid artery resulted in platelet adherence to the underlying subendothelium. This platelet accumulation on the damaged vessel wall was greatly reduced by clopid ogrel: 95% (P<.001) inhibition of platelet adhesion after a single ora l dose of 25 mg/kg. Ticlopidine (200 mg/kg) was also effective (71% in hibition; P<.001), whereas aspirin (100 mg/kg PO) failed to reduce pla telet adhesion to the subendothelium. The effect of clopidogrel on int imal smooth muscle hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was then investigated. After a 16-day t reatment, clopidogrel (25 mg/kg per day PO) inhibited the development of intimal thickening (48% inhibition; P<.01). This effect was dose de pendent and increased with the duration of the treatment. Under the sa me experimental conditions, ticlopidine (200 mg/kg per day PO) inhibit ed myointimal thickening (57%; P<.001), whereas aspirin was ineffectiv e. These results show that clopidogrel and ticlopidine, two ADP-select ive antiplatelet agents, can reduce myointimal thickening after endoth elial injury. This effect can be due to the inhibition of platelet adh esion and aggregation to the exposed subendothelium.