Development of eptifibatide

The primary cause of acute coronary syndromes is the development of a thrombus, a pathologic manifestation of platelet aggregation that occurs as part of the normal process of hemostasis. The discovery that the final common step in platelet aggregation, through the binding of fibrinogen to the activated platelet integrin glycoprotein (GP) IIb/IIIa, has opened the door to the development of novel and potentially more effective antithrombotic therapies. Abciximab, a human-murine chimeric Fab fragment of a monoclonal antibody against the GP IIb/IIIa receptor, was the first agent of this class to demonstrate clinical effectiveness. Several of the specific properties of abciximab, such as its long half-life, lack of receptor-blocking specificity, and some tendency for antigenicity, have prompted the development of alternative GP IIb/IIIa inhibitors with distinct pharmacologic profiles.

One of these newer agents is eptifibatide, which was developed by mimicking the GP IIb/IIIa blocker barbourin, found in the venom of the southeastern pigmy rattlesnake. Eptifibatide is a small, cyclic heptapeptide that has shown high specificity and high affinity for GP IIb-IIIa, a short plasma half-life, and rapid onset of antiplatelet action accompanied by a rapid reversibility of platelet inhibition once treatment is stopped.

In clinical trials, culminating in the phase III IMPACT II (Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis) and PURSUIT (Platelet GP IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trials, eptifibatide was found to reduce coronary events significantly in a broad range of low-, medium-, and high-risk patients with acute coronary syndromes without significantly increasing the risk of bleeding or other complications. These results suggest that eptifibatide may prove to be an effective addition to currently available antithrombotic therapies.