Anti-GPIIb/IIIa drugs: Current strategies and future directions

Three platelet glycoprotein (GP) IIb/lIIa receptor antagonists have been ap proved as adjunctive therapy to decrease the ischemic complications of perc utaneous coronary interventions (PCI) and/or unstable angina. They include the chimeric murine/human monoclonal antibody 7E3 Fab fragment (abciximab), a cyclic heptapeptide based on the KGD amino acid sequence (eptifibatide), and a nonpeptide mimetic of the RGD sequence (tirofiban). The agents are v ery effective in providing both short-term and long-term benefit after PCI, and one agent has also demonstrated a progressive long-term mortality bene fit. The long-term mortality benefit is highly cost-effective when compared to other medical interventions. The benefits in treating unstable angina w ithout PCI are less dramatic and robust, with some agents providing no bene fit. Severe thrombocytopenia is an infrequent, but potentially serious, com plication of therapy with all of the agents. The risk of major bleeding is increased only minimally or not at all by the drugs. Currently, a number of new indications for GPIIb/IIIa antagonists are under study, including acut e myocardial infarction (+/- thrombolytic therapy, +/- PCI) and stroke. In addition to their impact on improving outcome, the results of clinical tria ls with these agents provide crucial insights into the contribution of GPII b/IIIa-mediated platelet function in the pathophysiology of thrombotic vasc ular disease.