Serruys Patrick W, Sianos Georgios, Abizaid Alexandre, Aoki Jiro, den Heijer Peter, Bonnier Hans, Smits Pieter, McClean Dougal, Verheye Stefan, Belardi Jorge, Condado Jose, Pieper Michel, Gambone Louise, Bressers Marco, Symons Janette, Sousa Eduardo, Litvack Frank
Erasmus Medical Center, Rotterdam, the Netherlands.
J Am Coll Cardiol. 2005 Jul 19;46(2):253-60. doi: 10.1016/j.jacc.2005.03.069.
The aim of this study was to evaluate the effect of variable dose and release kinetics of paclitaxel on neointimal hyperplasia.
Conventional paclitaxel-eluting stents use a durable polymer coating as a vehicle for drug delivery. The Conor stent (Conor Medsystems, Menlo Park, California) with intra-strut wells and erodable polymer is specifically designed for drug delivery with programmable pharmacokinetics.
Two hundred and forty-four patients with single vessel disease received either a bare metal Conor stent (n = 53) or one of six different release formulations that varied in dose (10 or 30 microg) and elution release kinetics (first order, zero order), direction (abluminal, luminal), and duration (5, 10, and 30 days). End points at six months (bare stent group) and at four months (eluting stent groups) were angiographic late loss and neointimal tissue volume by intravascular ultrasound and the rate of major adverse cardiac events (MACE).
The lowest in-stent late loss (0.38 mm, p <0.01, and 0.30 mm, p <0.01) and volume obstruction (8%, p <0.01, and 5%, p <0.01) were observed with the 10-microg and 30-microg doses in the 30-day release groups respectively, whereas the highest in-stent late loss (0.88 mm), volume obstruction (26%), and restenosis rate (11.6%) were observed in the bare stent group. The overall MACE rate of the eluting stent group was 8.6%: death 0.5%, myocardial infarction 2.7%, and target lesion revascularization (TLR) 5.3%. Sub-acute thrombosis was 0.5%. The TLR rates in the two 30-day release groups were 0% and 3.4%.
This novel eluting stent platform, using an erodable polymer with complete elution of low doses of paclitaxel, is safe. The inhibition of the in-stent neointimal hyperplasia was best in the long release groups.
本研究旨在评估紫杉醇的可变剂量和释放动力学对新生内膜增生的影响。
传统的紫杉醇洗脱支架使用耐用的聚合物涂层作为药物递送载体。带有支架内微孔和可降解聚合物的Conor支架（Conor Medsystems，加利福尼亚州门洛帕克）专门设计用于具有可编程药代动力学的药物递送。
244名单支血管病变患者接受了裸金属Conor支架（n = 53）或六种不同释放制剂中的一种，这些制剂在剂量（10或30微克）、洗脱释放动力学（一级、零级）、方向（血管外膜、管腔）和持续时间（5、10和30天）方面有所不同。六个月时（裸支架组）和四个月时（洗脱支架组）的终点为血管造影晚期管腔丢失和血管内超声检测的新生内膜组织体积以及主要不良心脏事件（MACE）发生率。
在30天释放组中，分别使用10微克和30微克剂量时观察到最低的支架内晚期管腔丢失（0.38毫米，p <0.01，和0.30毫米，p <0.01）和体积阻塞（8%，p <0.01，和5%，p <0.01），而在裸支架组中观察到最高的支架内晚期管腔丢失（0.88毫米）、体积阻塞（26%）和再狭窄率（11.6%）。洗脱支架组的总体MACE发生率为8.6%：死亡0.5%，心肌梗死2.7%，靶病变血管重建（TLR）5.3%。亚急性血栓形成率为0.5%。两个30天释放组的TLR发生率分别为0%和3.4%。
这种新型洗脱支架平台，使用可降解聚合物并完全洗脱低剂量紫杉醇，是安全的。在长期释放组中，对支架内新生内膜增生的抑制效果最佳。
