The risk and benefit ratio of glycoprotein IIb/IIIa inhibitors with dual oral antiplatelet therapy after failed thrombolysis and rescue percutaneous coronary intervention (PCI) is unclear. Using a randomized placebo-controlled, double-blind design, we compared intravenous (IV) and intracoronary (IC) abciximab delivery in 74 patients referred for rescue transradial PCI. The primary angiographic end points were the final thrombolysis in myocardial infarction flow and myocardial blush grades. Secondary end points included acute and 6-month outcomes using angiographic parameters, platelet aggregation parameters, cardiac biomarkers, cardiac magnetic resonance measurements (CMR) and clinical end points. After rescue PCI, normal thrombolysis in myocardial infarction 3 flows were obtained in 70% in the IC group, 48% in the IV group, and 71% in the placebo group, respectively (p = 0.056). Final myocardial blush grades 2 and 3 were obtained in 43% and 39% in the IC group, 48% and 26% in the IV group, and 46% and 42% in the placebo group (p = 0.67), respectively. Acutely, peak release of cardiac biomarkers, necrosis size, myocardial perfusion and no-reflow as assessed by CMR, and clinical end points were similar between the groups and did not suggest a benefit for IC or IV abciximab compared with placebo. There was no increase in bleeding or access site-related complications with abciximab compared with placebo. Clinical, angiographic, and CMR outcomes at 6 months remained comparable between the groups. In patients with ST-elevation myocardial infarction presenting with failed thrombolysis undergoing transradial rescue PCI, IC or IV abciximab had no significant clinical impact.

An unexpectedly high incidence of thrombosis in patients that received the polylactic acid bioresorbable vascular scaffold (BVS) suggests a delayed/incomplete endothelial repair with this stent. The anti-platelet agent tirofiban stimulates endothelial cell migration and proliferation, mediated by VEGF production. We investigated the tirofiban effect on the migration and adhesion of endothelial cells to BVS, in vitro. We performed human umbilical endothelial cell (HUVEC) cultures in the presence of BVS. Tirofiban, similarly to VEGF, increased the ability of HUVEC to grow on the vascular scaffold, compared to unstimulated or abciximab-treated cells. Tirofiban increased HUVEC expression of β1 and β3 integrins along with collagen and fibronectin. A role for β1 integrin in the "pro-adhesive and -migratory" signals elicited by tirofiban was suggested by use of an anti-β1-blocking antibody that prevented poly-levo-lactic acid vascular scaffold colonization. Our study suggests that tirofiban may improve the outcomes of patients receiving BVS by accelerating stent endothelization.

Abciximab has been studied in three phase 3 clinical trials: EPIC, EPILOG, and CAPTURE. 

Abciximab is a glycoprotein IIb/IIIa receptor antagonist that functions to prevent platelet aggregation, thus reducing thrombus initiation and propagation. It has been widely used during percutaneous endovascular interventions, such as aneurysm coil embolization, angioplasty, atherectomy, and stent placement, as both a preventative and a salvage therapy. The use of abciximab in cardiac and neurosurgical procedures has been associated with a reduced incidence of ischemic complications and a decreased need for repeated intervention. In these settings, abciximab has been delivered transarterially via a microcatheter or infused intravenously for systemic administration. The authors describe novel in situ delivery of abciximab as an agent to dissolve "white clots," which are composed primarily of platelets, during an intracranial superficial temporal artery to middle cerebral artery bypass in a 28-year-old woman with severe intracranial occlusive disease. Abciximab was able to resolve multiple platelet-based clots after unsuccessful attempts with conventional clot dispersal techniques, such as heparinized saline, tissue plasminogen activator, mechanical passage of a wire through the vessel lumen, and multiple takedowns and re-anastomosis. After abciximab was administered, patency was demonstrated intraoperatively using indocyanine green dye and confirmed postoperatively at 1 and 10 months via CT angiography. The in situ use of abciximab as an agent to disperse a thrombus during intracranial bypass surgery is novel and has not previously been described in the literature, and serves as an additional tool during intracranial vessel bypass surgery.

Platelet integrin receptor αIIbβ3 supports platelet aggregation by binding fibrinogen. The interaction between the fibrinogen C-terminal γ-chain peptide composed of residues γ-404-411 (GAKQAGDV) and the Arg-Gly-Asp (RGD) binding pocket on αIIbβ3 is required for fibrinogen-mediated platelet aggregation, but data suggest that other ancillary binding sites on both fibrinogen and αIIbβ3 may lead to higher-affinity fibrinogen binding and clot retraction. To identify additional sites, we analyzed the ability of platelets and cells expressing normal and mutant αIIbβ3 to adhere to an immobilized fibrinogen plasmin fragment that lacks intact γ-404-411 ('D98'). We found the following: (1) Activated, but not unactivated, platelets adhere well to immobilized 'D98.' (2) Cells expressing constitutively active αIIbβ3 mutants, but not cells expressing normal αIIbβ3 or αVβ3, adhere well to 'D98.' (3) Monoclonal antibodies 10E5 and 7E3 inhibit the adhesion to 'D98' of activated platelets and cells expressing constitutively active αIIbβ3, as do small-molecule inhibitors that bind to the RGD pocket. (4) EDTA paradoxically induces normal αIIbβ3 to interact with 'D98.' Because molecular modeling and molecular dynamics simulations suggested that the αIIb L151-D159 helix may contribute to the interaction with 'D98,' we studied an αIIbβ3 mutant in which the αIIb 148-166 loop was swapped with the corresponding αV loop; it failed to bind to fibrinogen or 'D98.' Our data support a model in which conformational changes in αIIbβ3 and/or fibrinogen after platelet activation and the interaction between γ-404-411 and the RGD binding pocket make new ancillary sites available that support higher-affinity fibrinogen binding and clot retraction.