El Khoury Rym, Tzvetanov Ivan, Estrada Edward A, McCarroll Edward, Goor Jared B, Guy Louis-Georges, Laflamme Martin, Schwartz Lewis B
Efemoral Medical, Inc., Los Altos, CA.
Charles River Laboratories, Boisbriand, Quebec, Canada.
JVS Vasc Sci. 2023 Jun 8;4:100114. doi: 10.1016/j.jvssci.2023.100114. eCollection 2023.
Recanalization with balloon angioplasty and/or self-expanding stents (SES) has become the endovascular treatment of choice for symptomatic femoropopliteal occlusive disease. These strategies generate suboptimal clinical results, however, because they fail to expand the artery fully and ineffectively prevent recoil, neointimal hyperplasia, and restenosis. Balloon-expandable stents, given their greater radial force and rigid structure, represent a more effective treatment strategy, but only short lengths can be implanted safely in arteries that deform and bend with skeletal motion. The purpose of this preclinical experiment was to test the hypothesis that simultaneous implantation of a series of short, resorbable, balloon-expandable, paclitaxel-eluting scaffolds would prevent neointimal hyperplasia and stenosis compared with SES in an animal model of percutaneous femoropopliteal intervention.
We extruded 6 × 60 mm Efemoral Vascular Scaffold Systems (EVSS) from copolymers of poly-L-lactic acid, coated with paclitaxel 3 μg/mm, crimped onto a single delivery balloon, and implanted percutaneously into the iliofemoral arteries of eight Yucatan mini-swine. We implanted 7- to 8-mm × 60 mm SES into the contralateral experimental arteries. The animals were serially imaged with contrast angiography and optical coherence tomography after 30, 90, 180, 365, and 730 days. The primary end point of this study was neointimal morphometry over time. Secondary end points included acute deformation and angiographic and optical coherence tomography-derived measurements of chronic vascular response.
Over the 2-year study period, one SES was found to be completely occluded at 90 days; all EVSS were widely patent at all time points. Arteries treated with SES exhibited profound neointimal hyperplasia with in-stent stenosis. In contrast, arteries treated with EVSS exhibited only modest vascular responses and minimal stenosis. After 2 years, the mean neointimal thickness (0.45 ± 0.12 vs 1.31 ± 0.91 mm; < .05) and area (8.41 ± 3.35 vs 21.86 ± 7.37 mm; < .05) were significantly decreased after EVSS implantation. By 2 years, all scaffolds in all EVSS-treated arteries had resorbed fully.
In this preclinical animal model of peripheral endovascular intervention, the EVSS decreased neointimal hyperplasia and stenosis significantly compared with SES, then dissolved completely between the first and second years after implantation.
球囊血管成形术和/或自膨式支架（SES）再通术已成为有症状的股腘动脉闭塞性疾病的血管内治疗选择。然而，这些策略产生的临床效果并不理想，因为它们无法充分扩张动脉，且不能有效预防回缩、新生内膜增生和再狭窄。球囊扩张式支架由于其更大的径向力和刚性结构，代表了一种更有效的治疗策略，但在随骨骼运动而变形和弯曲的动脉中，只能安全植入较短的长度。本临床前实验的目的是检验以下假设：在经皮股腘动脉介入动物模型中，与SES相比，同时植入一系列短的、可吸收的、球囊扩张式、紫杉醇洗脱支架可预防新生内膜增生和狭窄。
我们用聚-L-乳酸共聚物挤出6×60mm的股动脉血管支架系统（EVSS），涂覆3μg/mm的紫杉醇，压接到单个输送球囊上，并经皮植入8只尤卡坦小型猪的髂股动脉。我们将7至8mm×60mm的SES植入对侧实验动脉。在30、90、180、365和730天后，用造影血管造影和光学相干断层扫描对动物进行连续成像。本研究的主要终点是随时间变化的新生内膜形态学。次要终点包括急性变形以及造影血管造影和光学相干断层扫描得出的慢性血管反应测量值。
在为期2年的研究期内，发现1个SES在90天时完全闭塞；所有EVSS在所有时间点均广泛通畅。接受SES治疗的动脉出现了严重的新生内膜增生和支架内狭窄。相比之下，接受EVSS治疗的动脉仅表现出适度的血管反应和最小程度的狭窄。2年后，EVSS植入后新生内膜的平均厚度（0.45±0.12 vs 1.31±0.91mm；P<0.05）和面积（8.41±3.35 vs 21.86±7.37mm；P<0.05）显著降低。到2年时，所有接受EVSS治疗的动脉中的支架均已完全吸收。
在这个外周血管内介入的临床前动物模型中，与SES相比，EVSS显著降低了新生内膜增生和狭窄，然后在植入后的第一和第二年之间完全溶解。
