Are we making efficient use of clopidogrel?

Blood platelets play a major role in the occurrence of thrombotic complications after percutaneous coronary interventions (PCI). Introduction of the thienopyridine drug ticlopidine as an adjunctive antiplatelet therapy has considerably improved the outcome of patients who undergo PCI. Thienopyridines act via blockade of one (P2Y12) of the three adenosine 50-diphosphate (ADP) receptors, reducing ADP-induced platelet activation and aggregation. Concerns about the side effects of ticlopidine, especially severe neutropenia and thrombotic thrombocytopenic purpura, were a major reason for the rapid replacement of this drug with clopidogrel. Another important limitation of ticlopidine is its delayed onset of action, with maximum inhibition of ADP-induced platelet aggregation achieved only several days after administration. Rapid inhibition of platelet aggregation is crucial for the prevention of post-interventional ischaemic complications, as demonstrated by the use of glycoprotein IIb/ IIIa inhibitors during coronary artery stenting. Clopidogrel, a newer thienopyridine derivative, has advantages over ticlopidine such as its better safety profile and quicker onset of action. Clopidogrel is not active in vitro and its hepatic biotransformation by cytochrome P450 (CYP) 3A4 produces as yet ill-defined active metabolite(s) with antiaggregatory effects.4 Depending on the dose used, the maximal effect of clopidogrel is achieved within a few hours (>300 mg)5 to several days (75 mg).4 The inhibition of aggregation lasts 8–10 days, which corresponds to platelet life span. Apart from the dose-dependence of