van der Giessen Wim J, Sorop Oana, Serruys Patrick W, Peters-Krabbendam Ilona, van Beusekom Heleen M M
Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.
JACC Cardiovasc Interv. 2009 Apr;2(4):284-90. doi: 10.1016/j.jcin.2008.12.012.
The aim of this study was to compare efficacy of low- and high-dose sirolimus release (25, 40, or 100 microg) from hydroxyapatite (HAp) with Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) (111 microg sirolimus) in porcine coronary arteries.
Polymer-based sirolimus-eluting stents such as Cypher interfere with vascular healing, probably due to the permanent presence of the polymer coating and the high sirolimus dose. The use of low-dose sirolimus and inert nonpolymeric but biodegradable coatings such as HAp might be more appropriate.
Stents (n = 68) were implanted, guided by quantitative coronary angiography. All swine received clopidogrel and acetylsalicylic acid during 28 days follow-up. Safety of the coating in absence of drugs was studied by comparing HAp with and without a lipid-based release regulating layer (HApR) with bare-metal stents. Efficacy was studied by comparing the release of 25, 40, and 100 microg sirolimus with Cypher.
The safety study (without drug) revealed no differences in neointimal thickening in response to HAp and HApR with complete healing in all groups. Dose response analysis showed that neointimal thickening was similar in all groups regardless of sirolimus dose, with a normal appearance of the endothelium. There was, however, a dose-dependent increase in fibrinoid (p = 0.028), considered to be a marker of delayed healing. The Cypher stent induced the highest amount of fibrinoid.
Reducing the dose of sirolimus eluting from a biocompatible HAp coated stent reduces signs of delayed vascular healing, without affecting neointimal hyperplasia.
本研究旨在比较羟基磷灰石（HAp）释放低剂量和高剂量西罗莫司（25、40或100微克）与Cypher支架（科迪斯公司，强生公司，新泽西州沃伦）（111微克西罗莫司）在猪冠状动脉中的疗效。
基于聚合物的西罗莫司洗脱支架，如Cypher支架，会干扰血管愈合，这可能是由于聚合物涂层的永久存在以及高剂量的西罗莫司。使用低剂量西罗莫司和惰性非聚合物但可生物降解的涂层，如HAp，可能更为合适。
在定量冠状动脉造影引导下植入68个支架。所有猪在28天的随访期间接受氯吡格雷和乙酰水杨酸治疗。通过比较有和没有脂质基释放调节层的HAp（HApR）与裸金属支架，研究了无药物情况下涂层的安全性。通过比较25、40和100微克西罗莫司与Cypher支架的释放情况，研究了疗效。
安全性研究（无药物）显示，HAp和HApR组内膜增厚无差异，所有组均完全愈合。剂量反应分析表明，无论西罗莫司剂量如何，所有组内膜增厚情况相似，内皮外观正常。然而，类纤维蛋白有剂量依赖性增加（p = 0.028），被认为是愈合延迟的标志。Cypher支架诱导的类纤维蛋白量最高。
减少生物相容性HAp涂层支架中西罗莫司的洗脱剂量可减少血管愈合延迟的迹象，而不影响内膜增生。
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