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A critical appraisal of platelet glycoprotein IIb/IIIa inhibition

^a Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

View larger version (13K): [in a new window]   Figure 1 Overview of intravenous glycoprotein IIb/IIIa trials by pooled analysis, with respect to 30-day death or myocardial infarction. Relative risk ratios for treatment with glycoprotein IIb/IIIa inhibitors as adjunctive therapy for percutaneous coronary intervention (PCI) and as empiric therapy for acute coronary syndromes (ACS) with electrocardiographic evidence of ischemia.

View larger version (33K): [in a new window]   Figure 2 Platelet glycoprotein IIb/IIIa structure and function. Heterodimeric structure with cation binding sites, RGD, KGD and KQAGDV binding sites and intracellular tail mediating both inside-to-outside and outside-to-inside signaling. Inside-out signals lead to increased platelet glycoprotein IIb/IIIa receptor activation, while outside-in signals increase ligand-induced binding site (LIBS) expression and cytoskeletal responses.

View larger version (21K): [in a new window]   Figure 3 Increased apoptosis activity with oral RGD glycoprotein IIb/IIIa inhibitors. (A) Time dependent increase in apoptosis in rat neonatal cardiomyocytes over 24 to 72 h. (B) Dose-dependent increase in apoptosis in rat neonatal cardiomyocytes observed with low-dose (3 µM), moderate-dose (10 µM) and high-dose (30 µM) of orbofiban or xemilofiban. *p < 0.01; p < 0.001. Reproduced with permission from Adderley et al (46).

View larger version (24K): [in a new window]   Figure 4 Divergence in platelet inhibition with abciximab with increasing time. Divergence in platelet inhibition with increasing infusion duration (52). Late variation in platelet inhibition may contribute to increased periprocedural events as seen in CAPTURE when compared with EPIC, EPILOG and EPISTENT. CAPTURE = C7E3 FAB Anti Platelet Therapy in Unstable Refractory Angina; EPIC = Evaluation of c7E3 for the Prevention of Ischemic Complications; EPILOG = Evaluation in PTCA to Improve Long-term Outcome with Abciximab GP IIb/IIIa blockade; EPISTENT = Evaluation of IIb/IIIa Platelet Inhibitor for Stenting.