Novel anti-inflammatory salicylate-based bioabsorbable drug-eluting polymeric stent coating

Abstract

Background: Permanent polymers used in current drug-eluting stent (DES) can trigger inflammatory reactions contributing to increased risk of late thrombosis and rebound restenosis. Optimal polymer selection and the use of completely absorbable polymers are expected to minimize these risks. Aim: To evaluate a novel potentially innately anti-inflammatory, salicylatebased bioabsorbable polymer eluting sirolimus in a clinically relevant animal model. Methods: Four different types of stents (n=36) were implanted in coronary arteries of 12 pigs using QCA to optimize stent apposition: bare metal stents (BMS); salicylic acid/adipic acid bioabsorbable polymer-only coated stents (SA/AA); Cypher stents; and metal stents coated with salicylic acid/adipic acid bioabsorbable polymer containing sirolimus (SA/AA+S). Dose density of sirolimus was 8.3 μg/mm of stent length, with in vitro studies demonstrating elution over 30 days and complete polymer degradation in 4–6 weeks. Animals were terminated at 1 month after angiographic restudy, for histopathologic and histomorphometric analyses. Results: Both SA/AA+S and Cypher stents had significantly lower angiographic % stenosis than BMS and SA/AA polymer-only groups (6±4% and 5±4% vs. 15±7% and 16±5%, respectively, Pb.001). Intimal thickness was lower for SA/AA+S and Cypher than for BMS (0.14±0.06 and 0.13±0.04 vs. 0.23±0.05 mm, respectively, Pb.001). Histologic % area stenosis was also lower for SA/AA+S and Cypher than for BMS (22±7% and 23±6% vs. 33±5%, respectively, Pb.001). The inflammatory reaction to SA/AA and to SA/AA+S was mild, whereas inflammation in BMS and Cypher tended to be more pronounced (P=.072). Conclusions: This study showed favorable vascular compatibility and efficacy of a novel anti-inflammatory salicylate-based biodegradable polymer eluting sirolimus. Since there is a tendency for reduced vessel wall inflammatory response and this polymer is fully absorbable, there may be significant improvement over existing DES to avoid late stent thrombosis.