After their introduction 2 decades ago, intravenous antagonists of the platelet glycoprotein IIb/IIIa (GPIs) (2) receptor quickly became the most researched intervention in cardiology, with numerous studies performed in a variety of clinical scenarios, ranging from adjunctive therapy to PCI in stable patients to primary PCI for STEMI (3- 4). Tens of thousands of patients with varying clinical profile and acuity have been enrolled in pre- and post-marketing studies of GPIs. The prototypical agent, abciximab, is a large, chimeric antibody to the glycoprotein (GP) receptor, which sterically hinders its binding to fibrinogen in a nearly irreversible fashion, preventing platelet aggregation and potentially promoting deaggregation of recently formed platelet-rich thrombi, as occurs in STEMI (5- 6). Initially, there was considerable enthusiasm about the “pleiotropic” effects of abciximab, such as inhibition of the vitronectin receptor and prevention of white blood cells aggregation to platelets and to the vascular wall (7). These interactions were hypothesized to lead to less restenosis and inflammation after PCI. Subsequent laboratory work resulted in the synthesis of smaller, cheaper molecules (peptides and nonpeptides), which bind specifically and reversibly to the receptor and allow for quicker recovery of platelet function after discontinuation of infusion. As compared with abciximab's long clearance time of 12 to 24 h, these small molecules had a clearance time of only 2 to 2.5 h, making them particularly attractive when urgent reversal of their effect was desirable. When administered in a dose sufficient to inhibit platelet aggregation by at least 80%, these compounds proved equally able as abciximab to inhibit shedding of soluble CD40 ligand, a compound associated with increased inflammation and restenosis after PCI (8).