Current treatments for acute coronary syndromes including unstable angina and non-ST-elevation myocardial infarction now include agents aimed at inhibiting platelet activation, adhesion, and aggregation with fibrinogen cross-linking. Two classes of drugs exist that inhibit these platelet effects at the level of the glycoprotein (GP) IIb/IIIa receptor on the platelet surface membrane. The first group are the thienopyridines (clopidogrel and ticlopidine). These drugs block GP IIb/IIIa complex activation by inhibiting adenosine diphosphate (ADP) binding to the platelet receptor. These oral agents have a slower onset and longer-term treatment duration. The CURE, TARGET, CREDO, and STAIG trials have demonstrated a 21% to 46% improvement in primary cardiac end points attributed to the addition of a thienopyridine. Significant benefits were demonstrated with the addition of clopidogrel to aspirin among patients undergoing percutaneous coronary interventions (PCI) (4.5 % versus 6.4% cardiovascular death, myocardial infarction, or urgent revascularization).

The second group of drugs are the direct GP IIb/IIIa antibodies or receptor antagonists (abciximab, tirofiban, and eptifibatide). These drugs inhibit the final pathway of platelet aggregation via fibrinogen cross-linking. Abciximab is a monoclonal antibody with a high affinity for both activated and resting platelets, whereas eptifibatide and tirofiban are nonantibody receptor inhibitors with less affinity for resting platelets and much faster dissociation rates (shorter half-lives) than abciximab. Meta-analysis of several large clinical trials (PRISM, PURSUIT, PARAGON, CAPTURE, and GUSTO-IV) has suggested only a modest 12% overall survival benefit attributable to the use of direct GP IIb/IIIa inhibitors when added to other therapeutics in acute coronary syndromes. Several subpopulations of high-risk patients, however, may have significantly improved outcome due to these agents. These include patients receiving emergent percutaneous interventions (34% reduction in primary end points versus 7% without GP IIb/IIIa), patients with raised troponin levels (58% reduced mortality versus 5% increase), and diabetic patients, in whom the greatest increase in survival was demonstrated. Of interest to physicians is

that women who receive GP IIb/IIIa inhibitors appear to have a 14% increase in combined end points as compared with men.