Summary
We investigated the comparative antithrombotic properties of clopidogrel, an analogue
of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs.
On each animal, clopidogrel or aspirin were used to treat the thrombotic process on
the left femoral artery and to prevent this process on the right femoral artery. Sequentially:
an injury and stenosis were carried out on the left femoral artery; the thrombotic
process was monitored with a Doppler during a 30-min observation period for cyclic
flow reductions or permanent cessation of flow; after the first cyclic flow reduction
occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine
(0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation
of flow; then injury and stenosis were applied on the right femoral artery. Before
and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo
platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore
any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were
efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened
(>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced
platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously
in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored
it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin
did not significantly prevent cyclic flow reductions which occurred in all animals
after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened
rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly
inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel
appears as a more potent antithrombotic drug than aspirin in this model, in treating
and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening
bleeding time.
