Combined aspirin and heparin is the most frequently used antiplatelet-antithrombotic therapy during coronary angioplasty to achieve and maintain activated clotting times (ACT) greater than 200 s. Because thrombin is generated during PTCA and potentially activates platelets, direct thrombin inhibitors (hirudin and hirulog) were developed as agents that could potentially inhibit platelet activation.
Despite these theoretical benefits, several multicenter trials have been unable to demonstrate that hirudin is a superior antithrombotic agent compared to heparin (143-148). Although hirudin has greater potential to reduce thrombin activity by inhibiting both fluid-phase and clot-bound thrombin, heparin has greater potential to inhibit earlier steps in the coagulation cascade. The net result may be an equal decrement in thrombus deposition within the culprit vessel. Although not significantly more efficacious than heparin, direct thrombin inhibitors may be safer than heparin.
Whereas there are multiple pathways for platelet activation, a single receptor (the Gp IIb/IIIa receptor) on the platelet surface mediates the final common pathway of platelet aggregation. By preventing the platelet Gp IIb/IIIa receptor from binding fibrinogen to cross-link platelets, Gp IIb/IIIa inhibitors exert potent effects during interventional procedures. There are three approved intravenous Gp IIb/IIIa antagonists presently available for use during PCI: abciximab (Reopro); eptifibatide (Integrilin); and tirofiban (Aggrastat). Each has a distinct biochemical profile, and trials of these drugs have shown varying effects. These medications have been tested in a variety of contexts including unstable angina, non-ST-segment elevation MI, ST-segment elevation MI, and PCI.
Abciximab is the Fab fragment of a human-mouse chimeric antibody directed against the Gp IIb/IIIa receptor. It has a high affinity for the receptor, and has a biological halflife of 8-12 h. It is cleared by the reticuloendothelial system and, therefore, is not affected by renal or hepatic dysfunction. Its activity is reversed by drug discontinuation and platelet transfusion. It is approved for use in primary PCI and refractory unstable angina with planned PCI within 24 h, but not in the routine medical management of patients with ACS.
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