Oral Platelet Glycoprotein IIb/IIIa Blockade

Oral antiplatelet therapy has demonstrated efficacy in reducing recurrent vascular ischemic events in patients with vascular disease (1, 2). Clinical evidence suggests that the benefit of secondary prevention is more widespread and extends beyond the regional circulation responsible for the signal vascular event to more generalized atherothrombotic manifestations. In support of the concept of widespread vascular benefit are data from the antiplatelet trialists collaboration, which show a 27% risk reduction in the composite outcome of myocardial infarction, ischemic stroke, and vascular death from a meta analysis of 145 clinical trials involving more than 73,000 high-risk patients in multiple disease categories (2, 3). Relative risk reductions for this composite outcome were 25% with aspirin and 33% with ticlopidine (2, 4, 5). Both ticlopidine and a chemically related compound, clopidogrel, block platelet activation by selectively and irreversibly inhibiting the binding of adenosine diphosphate (ADP) to its receptor on platelets, thus affecting ADP-mediated activation of the glycoprotein (GP) IIb/IIIa complex—the final common pathway for platelet activation (6–8). When compared with aspirin, these thienopyridine derivatives have achieved a further 8–10% risk reduction for the composite outcomes of stroke, myocardial infarction, and vascular death (9). Synergism for inhibition of collagen-induced platelet aggregation has been demonstrated for ticlopidine and aspirin (10). In addition, this combination has proven superior in reducing indices of platelet activation (11–13) and thrombotic clinical events (14, 15) in patients following coronary stent deployment when compared to therapy with aspirin alone or the combination of aspirin and coumadin anticoagulation.