CVPath Institute, Gaithersburg, MD, United States of America.
Medtronic CardioVascular, Santa Rosa, CA, United States of America.
Int J Cardiol. 2021 Mar 15;327:52-57. doi: 10.1016/j.ijcard.2020.11.030. Epub 2020 Nov 23.
Short-term dual antiplatelet therapy (DAPT) is a suitable strategy after stent implantation especially in patients at high risk for bleeding. The thromboresistant characteristics and the healing profile permanent polymer stents such as the Resolute Onyx- drug-eluting stent (DES) has never been tested against the current approved stents for short-term DAPT, the polymer free (PF) biolimus-eluting stent (PF-BES) and bare metal stents (BMS) in dedicated preclinical models.
An ex-vivo porcine arteriovenous shunt and in-vivo flow loop model were used to evaluate thromboresistance. The healing profile was assessed in the rabbit model at 28 days by confocal microscopy (CM), scanning electron microscopy (SEM) and histology. Onyx-DES was separately compared with Onyx-BMS in first experiment and PF-BES in second experiment.
In an ex-vivo shunt model, CM and SEM showed significantly less platelet adhesion for Onyx-DES relative to Onyx-BMS and PF-BES. In a flow loop model using human blood, platelet adhesion was also significantly less in Onyx-DES as compared to PF-BES and Onyx-BMS. In the healing study, Onyx-BMS showed significantly greater healing profile relative to Onyx-DES as expected, whereas Onyx-DES showed equivalent endothelial coverage by SEM and significantly less Evan's blue uptake and comparable colocalization of p120 and vascular endothelial-cadherin when compared with PF-BES.
Onyx-DES showed qualities of thomboresistance and healing which appear to be compatible with short-term DAPT. Thromboresistance was superior to PF-BES and healing was equivalent to PF-BES in this pre-clinical study. Onyx-DES might provide advantages when considering short-term DAPT especially in patients at high risk of bleeding.
短期双联抗血小板治疗(DAPT)是支架植入后的一种合适策略,尤其是在出血高风险患者中。具有抗血栓特性和愈合特性的永久性聚合物支架,如 Resolute Onyx-药物洗脱支架(DES),从未在专门的临床前模型中与目前批准的短期 DAPT 药物、无聚合物(PF)生物可吸收支架(PF-BES)和裸金属支架(BMS)进行过比较。
使用体外猪动静脉分流模型和体内血流回路模型来评估抗血栓形成能力。通过共聚焦显微镜(CM)、扫描电子显微镜(SEM)和组织学评估 28 天的愈合情况。在第一个实验中,Onyx-DES 分别与 Onyx-BMS 和 PF-BES 进行比较,在第二个实验中,Onyx-DES 与 PF-BES 进行比较。
在体外分流模型中,CM 和 SEM 显示 Onyx-DES 相对于 Onyx-BMS 和 PF-BES 血小板黏附明显减少。在使用人血的血流回路模型中,Onyx-DES 中的血小板黏附也明显少于 PF-BES 和 Onyx-BMS。在愈合研究中,Onyx-BMS 的愈合情况明显优于 Onyx-DES,这是预期的结果,而 Onyx-DES 通过 SEM 显示出相当的内皮覆盖,Evan's 蓝摄取明显减少,与 PF-BES 相比,p120 和血管内皮钙黏蛋白的共定位也相当。
Onyx-DES 表现出抗血栓形成和愈合的特性,这些特性似乎与短期 DAPT 兼容。在这项临床前研究中,Onyx-DES 的抗血栓形成能力优于 PF-BES,愈合能力与 PF-BES 相当。在考虑短期 DAPT 时,Onyx-DES 可能具有优势,特别是在出血高风险患者中。