Tirofiban in Interventional Cardiology

The discovery of the pivotal role played by the Arg-Gly-Asp (RGD) tripeptide sequence in the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor (1), coupled with the realization that the naturally occurring snake venom disintegrins also exerted their potent antiplatelet effect via the same RGD domain (2,3), led to the development of a series of nonpeptide RGD mimetics with increased specificity for the GPIIb/IIIa integrin (4,5). Subsequent nuclear magnetic resonance studies of one disintegrin, eichistatin, revealed that the key RGD unit resided in a loop segment of the protein with a distinct spatial arrangement (6). A specific search for a similarly structured peptidomimetic led to the discovery of a tyrosine analog inhibitor of GPIIb/IIIa (7). Terminal modification of this compound produced MK-383 (L-700,462; tirofiban), a GPIIb/IIIa inhibitor with substantially increased potency, as evidenced by a >2000-fold decrease in the median inhibitory concentration (IC50) (8,9). Tirofiban (Aggrastat®, Merck & Co., West Point, PA) is indicated for use in patients with acute coronary syndromes including those undergoing percutaneous coronary intervention (PCI). This chapter reviews the clinical use of tirofiban in interventional cardiology with emphasis on its use as primary therapy in PCI and as pretreatment in patients with an acute coronary syndrome prior to PCI. An integral part of this discussion will focus on the key trials, RESTORE and TARGET, that have helped define tirofiban’s role in interventional practice.