Abstract 4397: Pitavastatin Incorporated Nanoparticle-eluting Stents Attenuate In-stent Stenosis Without Anti-healing Effects Induced by Sirolimus-eluting Stents (cypher) in Porcine Coronary Artery Model
Background: The use of the currently marketed drug-eluting stent presents serious safety problems such as increased late thrombosis, which is thought to result mainly from the anti-healing effects (impaired re-endothelialization resulting in abnormal inflammation and fibrin deposition). We recently developed a bioabsorbable polymeric nanoparticle (NP)-eluting stent using a novel cation electrodeposition technology. Statins are known to inhibit proliferation of vascular smooth muscle cells (VSMC) and to promote vascular healing. We therefore hypothesized that statin-incorporated NP-eluting stent attenuates in-stent stenosis without anti-healing effects.
Methods and Results: Among 6 marketed statins, pitavastatin (Pitava) was found to be most potent effects on VSMC proliferation and endothelial regeneration in vitro. Pitavastatin also inhibited tissue factor expression in endothelial cells. We then formulated Pitava-NP-eluting stent (20 μg Pitava per stent). In pig coronary artery model, Pitava-NP-eluting stent attenuated in-stent stenosis as effective as polymer-coated sirolimus-eluting stent (Cypher) at 4 weeks post-stenting. In Cypher sites, anti-healing effects (defective endothelial regeneration, fibrin deposition, inflammation) were noted whereas the opposite pro-healing effects were observed in Pitava-NP-eluting stent sites (Figure⇓).
Conclusion: Pitava-NP-eluting stents attenuated in-stent stenosis as effective as SES without anti-healing effects seen with SES, and elicited pro-healing effects in porcine coronary artery model. This nanotechnology platform may be developed as a more effective and safer device in future.