Tellez Armando, Seifert Paul S, Donskoy Elina, Sushkova Natalia, Pennington Douglas E, Milewski Krzysztof, Krueger Christian G, Kaluza Greg L, Eppihimer Michael J, Huibregtse Barbara A, Dawkins Keith D, Granada Juan F
aSkirball Center for Cardiovascular Research at Cardiovascular Research Foundation, Orangeburg bColumbia University Medical Center, New York, New York cBoston Scientific Corporation, Natick, Massachusetts dDepartment of Animal Sciences, University of Wisconsin, Madison, Wisconsin, USA.
Coron Artery Dis. 2014 May;25(3):198-207. doi: 10.1097/MCA.0000000000000099.
The utility of animal models for the prediction of drug-eluting stent (DES) efficacy in human clinical trials is still unclear. The familial hypercholesterolemic swine (FHS) model has been shown to induce a human-like neointimal response to bare metal stent (BMS) implantation. However, its utility to discriminate efficacy signals following DES implantation is unknown. In this study, we aimed to test the efficacy and healing response of several everolimus-eluting stent (EES) platforms in the coronary territory of the FHS.
A total of 19 EES platforms (SYNERGY=6, SYNERGY½-dose=7, and PROMUS Element=6) and an identical BMS control (Element=6) were implanted into the coronary arteries of nine FHS. All implants were performed under intravascular ultrasound guidance using a 1.2 : 1 overstretch ratio. At 30 days, the vascular response to the implant was evaluated by quantitative coronary angiography, optical coherence tomography, and histology.
At 28 days, all EES platforms showed a significant decrease in angiographic late lumen loss (between 27 and 37%) compared with the BMS control group. This finding was confirmed both by optical coherence tomography (mean neointimal thickness=28-42% reduction) and by histology (mean neointimal thickness=44-55% reduction). All EES platforms showed similar degrees of neointimal inhibition. The presence of moderate to severe para-strut inflammation was observed in 83% of the stent sections in the BMS group compared with 28.6% in the SYNERGY½-dose group and 0% in the SYNERGY and PROMUS groups (P=0.0002). There was a 68-95% reduction in MMP9 expression in the media in all EES platforms compared with the BMS controls. The presence of mild to moderate para-strut fibrin deposits ranged from 66.7 to 83.4% in all EES platforms compared with 16.7% in the EBMS group.
The FHS coronary injury model showed the efficacy of several EES platforms compared with an identical BMS control. Everolimus eluted from different polymeric platforms showed lower levels of inflammation and slightly higher fibrin deposits compared with BMS controls.
动物模型在预测药物洗脱支架（DES）在人体临床试验中的疗效方面的效用仍不明确。家族性高胆固醇血症猪（FHS）模型已被证明对裸金属支架（BMS）植入可诱导类似人类的内膜增生反应。然而，其在区分DES植入后的疗效信号方面的效用尚不清楚。在本研究中，我们旨在测试几种依维莫司洗脱支架（EES）平台在FHS冠状动脉区域的疗效和愈合反应。
将总共19个EES平台（SYNERGY = 6个、SYNERGY半剂量 = 7个、PROMUS Element = 6个）以及一个相同的BMS对照（Element = 6个）植入9只FHS的冠状动脉。所有植入均在血管内超声引导下以1.2 : 1的过度扩张比例进行。在30天时，通过定量冠状动脉造影、光学相干断层扫描和组织学评估植入物的血管反应。
在28天时，与BMS对照组相比，所有EES平台的血管造影晚期管腔丢失均显著降低（降低27%至37%）。光学相干断层扫描（平均内膜厚度降低28%至42%）和组织学（平均内膜厚度降低44%至55%）均证实了这一发现。所有EES平台均显示出相似程度的内膜抑制。BMS组83%的支架节段观察到中度至重度支架旁炎症，而SYNERGY半剂量组为28.6%，SYNERGY和PROMUS组为0%（P = 0.0002）。与BMS对照组相比，所有EES平台中膜内MMP9表达降低了68%至95%。所有EES平台中轻度至中度支架旁纤维蛋白沉积的发生率在66.7%至83.4%之间，而EBMS组为16.7%。
与相同的BMS对照相比，FHS冠状动脉损伤模型显示了几种EES平台的疗效。与BMS对照相比，从不同聚合物平台洗脱的依维莫司显示出较低水平的炎症和略高的纤维蛋白沉积。
