Summary
Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to
the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage
is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet
aggregation in ambulatory patients with symptomatic atherosclerotic disease and it
prevents the recurrence of ischemic events more efficiently than aspirin. Its adequate
dose in more acute situations remained to be determined. Therefore, sixty two patients
with coronary artery disease were randomly assigned in four groups treated, within
24 h after coronary artery bypass graft, by clopidogrel 50 mg/od, 75 mg/od or 100
mg/od or by ticlopidine 250 mg/bid which was considered as the reference. The tolerance
of clopidogrel was fairly good during the whole period of the study. Bleeding time
and ex-vivo platelet aggregation induced by ADP 2 μM and 5 μM were performed at day
-1, +9 and +28 after surgery. Like ticlopidine, the three dose levels of clopidogrel
significantly inhibited ex-vivo platelet activity and prolonged the bleeding time
at day 28. However, unlike ticlopidine, the inhibitory effects of clopidogrel were
not significant at day 9, especially with 75 mg/od, a dose which was found to significantly
protect patients in a chronic situation. Hence, although the clinical outcome for
patients included in this limited study was the same in the four groups, these results
suggest that the dose regime of clopidogrel should be more extensively investigated
during the early period following coronary artery bypass graft, facing an overproduction
of young and hyperreactive platelets. By analogy, the dose regime should be also investigated
in other situations with an acute risk of arterial thrombotic occlusion.
Keywords
Platelets - clopidogrel - CABG surgery
