Antithrombotic potential of polymer-coated stents eluting platelet glycoprotein IIb/IIIa receptor antibody.
BACKGROUND
Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody (AZ1) was adsorbed onto cellulose polymer-coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody-eluting stents.


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 flow probes and platelet adhesion was ascertained by use of 111In-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 +/- 4.5 x 10(7)) than either base-polymer (32.1 +/- 4.3 x 10(7)) or anti-CMV-eluting (35.2 +/- 8.8 x 10(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.
Aggarwal
R K
RK
Division of Cardiology, Faculty of Medicine, University of Leicester, UK.
Ireland
D C
DC
Azrin
M A
MA
Ezekowitz
M D
MD
de Bono
D P
DP
Gershlick
A H
AH
D000327:Adsorption; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D003587:Cytomegalovirus / Q000276:immunology; D004867:Equipment Design; D005263:Femoral Artery / Q000502:physiology*; D007083:Iliac Artery / Q000502:physiology*; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D011817:Rabbits; D012039:Regional Blood Flow; D015607:Stents; D015912:Thrombolytic Therapy; D017539:Tunica Intima / Q000187:drug effects / Q000502:physiology; D017540:Tunica Media / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin