Yazdani Saami K, Sheehy Alexander, Nakano Masataka, Nakazawa Gaku, Vorpahl Marc, Otsuka Fumiyuki, Donn Rosy S, Perkins Laura E, Simonton Charles A, Kolodgie Frank D, Virmani Renu
CVPath Institute Inc, Gaithersburg, Maryland 20878, USA.
J Invasive Cardiol. 2013 Aug;25(8):383-90.
This study was designed to evaluate the pharmacokinetic and vascular healing of a second-generation everolimus-eluting stent (EES) and slow-release zotarolimus-eluting stent (R-ZES).
Second-generation DESs have alleviated the safety concerns of late stent thrombosis by addressing issues of polymer biocompatibility and stent design, and optimizing drug loads and release kinetics. No preclinical comparison study exists between these stents.
Rabbit iliac artery stent implantation was performed using Xience Prime EES and Resolute R-ZES. Histomorphometric evaluation was performed at 28 and 60 days after implantation in an induced atheroma model. Endothelial coverage and maturation were assessed by scanning electron microscopy and immuno-labeling at 14 and 28 days following deployment. For pharmacokinetic studies, arterial tissue and stents were retrieved at 3, 14, 28, and 90 days, and blood samples were obtained during the first 24 hours.
Vascular remodeling (percent stenosis, neointimal thickness) was similar in arteries implanted with either stent group. At 28 days, inflammation was significantly less in the EES group as compared to the R-ZES group (inflammation score: 1.59 ± 0.52 vs 2.22 ± 0.69, respectively; P=.044), with no differences observed at 60 days. Endothelial coverage was similar between both groups; however, endothelial maturation above stent struts was significantly higher in the EES group vs R-ZES group at 28 days (33 ± 20% vs 22 ± 21%, respectively; P=.040). Arterial drug level concentrations were also shown to be significantly less in the EES group vs the R-ZES group (P<.0001).
Overall, EES and R-ZES displayed similar remodeling properties with lower arterial drug levels observed in the EES group vs the R-ZES group, which may have led to more rapid endothelial maturation.
本研究旨在评估第二代依维莫司洗脱支架（EES）和缓释佐他莫司洗脱支架（R-ZES）的药代动力学及血管愈合情况。
第二代药物洗脱支架通过解决聚合物生物相容性和支架设计问题、优化药物负荷及释放动力学，缓解了晚期支架血栓形成的安全性担忧。目前尚无这两种支架之间的临床前比较研究。
使用Xience Prime EES和Resolute R-ZES对兔髂动脉进行支架植入。在诱导性动脉粥样硬化模型中，于植入后28天和60天进行组织形态计量学评估。在支架植入后14天和28天，通过扫描电子显微镜和免疫标记评估内皮覆盖和成熟情况。进行药代动力学研究时，在3天、14天、28天和90天取回动脉组织和支架，并在最初24小时内采集血样。
在植入任何一种支架组的动脉中，血管重塑（狭窄百分比、新生内膜厚度）相似。在28天时，EES组的炎症明显少于R-ZES组（炎症评分分别为1.59±0.52和2.22±0.69；P=0.044），在60天时未观察到差异。两组之间的内皮覆盖相似；然而，在28天时，EES组支架支柱上方的内皮成熟度明显高于R-ZES组（分别为33±20%和22±21%；P=0.040）。EES组的动脉药物水平浓度也明显低于R-ZES组（P<0.0001）。
总体而言，EES和R-ZES显示出相似的重塑特性，EES组的动脉药物水平低于R-ZES组，这可能导致内皮成熟更快。
