In vitro evaluation of c7E3-Fab (ReoPro (TM)) eluting polymer-coated coronary stents

Objective: Stent thrombosis and in-stent restenosis remain problematic in c ertain patient sub-groups. c7E3-Fab (ReoPro(TM), abciximab) inhibits the pl atelet glycoprotein IIb/IIIa receptor as well as the smooth muscle cell alp ha(v)beta(3) receptor, and thus may influence both processes, especially if high local concentrations could be achieved. We have studied the adsorptio n and elution characteristics of c7E3-Fab on commercially available polymer -coated stents. We have also investigated the effect of such antibody bindi ng on platelet deposition in vitro, and on antibody deposition into ex vivo human saphenous vein wall to assess whether such stents may influence sten t thrombosis and restenosis. Methods and results: Adsorption was measured u sing a radioisotope technique after immersing segments of polymer-coated st ents in c7E3-Fab solutions. Uptake was dependent on antibody concentration and duration of immersion of wire in the solution. After 22 h (at 5 mg ml(- 1)), 1146+/-101 ng cm(-1) wire was adsorbed. In an in vitro perfusion circu it, the antibody eluted slowly, with 53% remaining after 12 days washing. T o determine the value that such stents might have in clinical practise, ads orption to balloon-mounted stents was assessed at room temperature, using c ommercially available c7E3-Fab (2 mg ml(-1)). Efficacy of eluting c7E3-Fab was determined by measuring deposition of (111)-Indium platelets. Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3% compa red to controls (P = 0.018). Deployment of treated stents in ex vivo saphen ous vein resulted in the deposition of c7E3-Fab in the intima and media. Co nclusions: c7E3-Fab can be passively adsorbed onto polymer-coated stents. I t elutes slowly and in a predictable manner, significantly inhibiting plate let deposition in vitro. These studies pave the way to developing stent-bas ed delivery of a potent anti-platelet agent that may additionally affect sm ooth muscle cell activity. (C) 2000 Elsevier Science B.V. All rights reserv ed.