Abstract 16008: Improved Safety and Efficacy of a Novel Dual cRGD- and Everolimus-Coated Coronary Stent Compared to Everolimus-Eluting Stents in the Porcine Coronary Model

Abstract

Background: Re-endothelialization after drug-eluting stent implantation is delayed. Integrin-binding cyclic Arg-Gly-As p (cRGD) peptide-loaded stents offer potential for enhanced early and late endothelial recovery by endothelial progenitor cell (EPC) anchorage. Here, a novel dual cRGD and everolimus-eluting stent was compared to an everolimus-eluting stent. Methods: The porcine coronary overstretch model was employed for analysis of Multi-Link Tetra bare metal stents with or without a specific conformal, mechanically robust polymer coating based on an aromatic polyetherurethaneurea with a soft segment of polytetramethyleneoxide and a hard segment of diphenylmethane diisocyanate and mixed diamines covered by a control-release layer. Stents were coated with immobilized cRGD, everolimus or cRGD+everolimus on the biostable PEA-40 polymer surface coating. Isolated porcine EPCs were labeled with cell tracker and infused into coronary arteries immediately after stent implantation. cRGD or everolimus recovered mass was quantified, re-endothelialization was assessed by scanning electron microscopy and area stenosis was quantified. Results: cRGD and everolimus recovered mass from PEA-40 cRGD/everolimus stents possessed a slow release profile. Marked EPC recruitment to stents was evidenced after intracoronary infusion of fluorescence-labeled EPCs. In cRGD+everolimus loaded stents, in-stent cross sectional stenosis was reduced and re-endothelialization above stent struts was accelerated (p<0.05 for both) while re-endothelialization between struts was similar (p>0.05) as compared to both everolimus-loaded and bare-metal stents. Conclusions: PEA-40 is a reliable carrier for cRGD and everolimus; the novel PEA-40 dual cRGD and everolimus stent coating both everolimus-dependently decreases coronary stenosis as well as integrin-dependently accelerates stent strut re-endothelialization as compared to everolimus-eluting stents in the porcine coronary overstretch model. Therefore, the concerted acceleration of vascular healing by facilitated homing of circulating EPCs and distinct antiproliferatory properties of everolimus might transfer to an improvement of stent safety while stent efficacy is maintained.