Development of eptifibatide

Background The primary cause of acute coronary syndromes is the development of a thrombus, a pathologic manifestation of platelet aggregation that occ urs as part of the normal process of hemostasis. The discovery that the fin al common step in platelet aggregation, through the binding of fibrinogen t o the activated platelet integrin glycoprotein (GP) IIb/IIIa, has opened th e door to the development of novel and potentially more effective antithrom botic therapies. Abciximab, a human-murine chimeric Fab fragment of a monoc lonal antibody against the GP IIb/IIIa receptor, was the first agent of thi s class to demonstrate clinical effectiveness. Several of the specific prop erties of abciximab, such as its long half-life, lack of receptor-blocking specificity, and some tendency for antigenicity, have prompted the developm ent of alternative GP IIb/IIIa inhibitors with distinct pharmacologic profi les. Methods and Results One of these newer agents is eptifibatide, which was de veloped by mimicking the GP IIb/IIIa blocker barbourin, found in the venom of the southeastern pigmy rattlesnake. Eptifibatide is a small, cyclic hept apeptide that has shown high specificity and high affinity for GP IIb-IIIa, a short plasma half-life, and rapid onset of antiplatelet action accompani ed by a rapid reversibility of platelet inhibition once treatment is stoppe d. Conclusions In clinical trials, culminating in the phase III IMPACT II (Int egrilin to Minimize Platelet Aggregation and Coronary Thrombosis) and PURSU IT (Platelet GP IIb-IIIa in Unstable Angina. Receptor Suppression Using Int egrilin Therapy) trials, eptifibatide was found to reduce coronary events s ignificantly in a broad range of low-, medium-, and high-risk patients with acute coronary syndromes without significantly increasing the risk of blee ding or other complications. These results suggest that eptifibatide may pr ove to be an effective addition to currently available antithrombotic thera pies.