The glycoprotein (GP)IIb/IIIa receptor is an integrin protein with binding domains on both the exterior of the cell and the cytoplasm; thus, its activation interacts with external adhesion ligands and cytoskeletal proteins. This receptor is highly expressed on the platelets (approximately 80,000 receptors per platelet) [1], making it a natural target for platelet inhibition. Platelet adhesion is started by active platelet surface receptors interacting with subendothelial proteins (e.g., von Willebrand factor and collagen). This initial interaction creates a layer of platelets that recruit additional platelets primarily by the activation of the GPIIb/IIIa receptor. This pivotal role mediating platelet–platelet interaction represents the final common pathway for platelet aggregation [2]. GP inhibitors block the binding of fibrinogen to GPIIb/IIIa receptors blocking the thrombus formation by preventing platelet aggregation. The chimeric 7E3 Fab half murine, half human fragment (abciximab) inhibits the clot formation by blocking platelet aggregation when 80% of receptor blockade is achieved [3, 4]. Abciximab has been used extensively in clinical trials establishing its efficacy, safety, and broad applicability as adjunct to percutaneous coronary intervention (PCI). The instrumentation of the coronary artery causes plaque rupture, vascular thrombosis, and platelet activation [5] potentially triggering thrombotic complications. The use of abciximab in PCI has helped reduce periprocedural ischemic complications and in some high-risk cohorts even mortality [6, 7]. However, most of the studies were performed in the era before the widespread use of prolonged oral dual antiplatelet therapy (DAPT), and therefore, the patterns of abciximab use have drastically changed in the current PCI era. Furthermore, cost concerns and the availability of powerful oral antiplatelet such as clopidogrel, prasugrel, or ticagrelor [8, 9] that offer robust platelet inhibition have limited abciximab and other GPIIb/IIIa inhibitor use. Nevertheless, the current ACC/AHA/SCAI Guidelines recommend the use of abciximab (either systemic or intracoronary) in patients with ST-segment-elevation myocardial infarction (STEMI) (class IIa and IIb, respectively) and in patients with unstable angina/non-ST-segment-elevation myocardial infarction (NSTEMI) with high-risk features (e.g., elevated troponins) with or without clopidogrel pretreatment (class I and IIa, respectively); in patients with stable CAD, it yields a class IIa indication for those patients not pretreated with clopidogrel and a IIb indication for patients pretreated with clopidogrel and unfractionated heparin.

Abciximab in PCI: The EPIC, EPILOG, and EPISTENT trials

The EPIC trial [10] tested the effect of abciximab in patients undergoing high-risk coronary angioplasty. The primary 30-day end point was a composite of death, nonfatal myocardial infarction (MI), unplanned surgical revascularization, unplanned repeat percutaneous procedure, unplanned implantation of a coronary stent, or insertion of an intra-aortic balloon pump for refractory ischemia. There was a 35% reduction in the primary end point (12.8% vs. 8.3%, P = 0.008) in patients randomized to the bolus plus infusion group and a 10% reduction in the bolus alone group (12.8% vs. 11.5%, P = 0.43). However, there was an increase in bleeding episodes and transfusions (7% vs. 14%, p < 0.0001). Most of the events were at the vascular access site, and they were deemed to be secondary to the lack of use of weight-adjusted heparin therapy. Thus, the follow-up to this study was the EPILOG trial [11] that randomly assigned patients undergoing urgent or elective PCI to receive abciximab with standard-dose, weight-adjusted heparin (bolus of 100 U/kg); abciximab with low-dose, weight-adjusted heparin (70 U/kg); or placebo with standard-dose, weight-adjusted heparin. The primary 30-day end point was a composite of death, MI, or urgent revascularization. The event rate was 11.7% versus 5.2% in the abciximab with low-dose heparin (HR, 0.43 [95% CI, 0.30–0.60; P < 0.001]) and 5.4% in the abciximab with standard-dose heparin (HR, 0.45 [95% CI, 0.32–0.63; P < 0.001]). There were no differences in the risk of major bleeding, although minor bleeding was more frequent among patients receiving abciximab with standard-dose heparin. The next large interventional trial with abciximab was the EPISTENT trial [12] that tested the contemporary use of bare metal stents in patients randomly assigned to stenting plus placebo, stenting plus abciximab, or balloon angioplasty plus abciximab. The primary 30-day composite end point included death, MI, or need for urgent revascularization. The primary end point occurred in 10.8% versus 5.3% of the abciximab group (HR, 0.48 [95% CI, 0.33–0.69; p < 0.001]) and 6.9% in the balloon plus abciximab group (HR, 0.63 [0.45–0.88]; p = 0.007). Major bleeding occurred in 2.2% of the placebo-assigned patients, 1.5% in stent plus abciximab group, and 1.4% in balloon angioplasty plus abciximab group (p = 0.38). These results validated the use of abciximab in a widespread group of patients with or without the use of stents in the era before the widespread use of ticlopidine or clopidogrel.