Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody

Background Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIla antibody (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody-eluting stents. Methods and Results Twenty-three polymer-coated stents with AZ1 antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control polymer-coated stents adsorbed with either no antibody (base-polymer, n=12) or isotype matched irrelevant antibody (anti-CMV-eluting, n=11) by implantation into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits. In 13 animals (acute group), flow measurements were made with transit-time Bow probes and platelet adhesion was ascertained by use of In-111-labeled autologous platelets. In the other 10 animals (chronic group), stent occlusion was assessed macroscopically after they were killed 28 days after stenting. Arteries with AZ1-eluting stents had significantly less platelet deposition (15.8+/-4.5X10(7)) than either base-polymer (32.1+/-4.3x10(7)) or anti-CMV-eluting (35.2+/-8.8x10(7)) controls (ANOVA, P<.0001). Compared with base-polymer or anti-CMV-eluting controls, arteries with AZ1-eluting stents showed a marked reduction in cyclic blood flow variation (P<.0001) and a significantly greater mean blood flow 2 hours after stent deployment (P<.0001). There was a significant improvement in the patency rate of AZ1-eluting stents compared with controls at both 2 hours (92% versus 46%, P=.034) and 28 days (100% versus 40%, P=.015). Conclusions Platelet GP IIb/IIIa antibody eluting from polymer-coated stents reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow variation, and improves patency rates after stent implantation in a rabbit iliac artery model. Its potential for reducing stent-related thrombosis in humans warrants further evaluation.