新型单面刻槽生物可降解聚合物涂层雷帕霉素洗脱支架治疗冠状动脉原位病变的长期有效性和安全性

Long term safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus- eluting stent for the treatment of coronary de novo lesions

目的比较新型单面刻槽生物可降解聚合物涂层雷帕霉素洗脱支架（Firehawk支架）与永久聚合物涂层依维莫司洗脱支架（Xience V支架）治疗冠状动脉原位病变的长期有效性和安全性。 方法本研究（TARGETⅠ试验）是一项前瞻性、多中心、非劣效、随机对照研究，自2010年8月至2011年4月入选国内16家中心的原发、原位、单支、单处冠状动脉病变患者460例。靶病变目测直径狭窄≥70%，病变长度≤24 mm。采用基于计算机的中央随机系统，根据置入的支架将患者随机分为Firehawk支架组和Xience V支架组。观察两组术后9个月晚期管腔丢失及术后5年靶病变失败（TLF）、患者相关临床复合终点（PoCE）和支架内血栓形成。TLF定义为心原性死亡、靶血管相关心肌梗死和缺血驱动的靶病变血运重建复合终点；PoCE定义为全因死亡、所有心肌梗死和再次血运重建复合终点。 结果（1）460例患者中，2例患者因未置入支架而退出研究；Firehawk支架组共有227例患者，Xience V支架组共有231例患者。两组基本临床特征和病变特征差异均无统计学意义（P均〉0.05）。（2）Firehawk组术后9个月晚期管腔丢失非劣效于Xience V组[（0.13±0.24）mm比（0.13±0.18）mm，P＝0.94]。（3）其中442例（96.5%）患者完成5年临床随访。术后5年，Firehawk支架组与Xience V支架组的TLF发生率差异无统计学意义[6.0% （13/217）比6.7% （15/225），P＝0.77]；Firehawk支架组与Xience V支架组的PoCE发生率差异也无统计学意义[12.0%（26/217）比17.8% （40/225），P＝0.09]。（4）Kaplan-Meier法分析显示，术后5年Firehawk支架组和Xience V支架组的TLF累积事件率分别为5.7%和6.6%，差异无统计学意义（HR＝0.88，95%CI 0.42～1.84，P＝0.72）；Land-Mark分析显示，术后累积5年Firehawk支架组和Xience V支架组的TLF累积事件率分别为3.6%和4.4%，差异也无统计学意义（HR＝0.83，95%CI 0.34～2.00，P＝0.67）。Kaplan-Meier法分析显示，术后1～5年Firehawk支架组和Xience V支架组的PoCE累积事件率分别为11.4%和17.3%，差异无统计学意义（HR＝0.64，95%CI 0.39～1.04，P＝0.07）；Land-Mark分析显示，术后1～5年Firehawk支架组和Xience V支架组的PoCE累积事件率分别为8.4%和10.0%，差异无统计学意义（HR＝0.66，95%CI 0.40～1.10，P＝0.11）。（5）在术后5年随访中，Firehawk组未发生任何支架内血栓形成事件，Xience组在术后3年发生支架内血栓形成1例。 结论在治疗冠状动脉原位简单病变时，Firehawk支架具有与Xience V支架相同的长期有效性和安全性。临床试验注册北美临床试验注册中心，注册号为NCT01196819。

ObjectiveTo compare the long term safety and efficacy of the novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent（Firehawk stent） and permanent polymer coating everolimus eluting stent（Xience V stent） for the treatment of coronary de novo lesions. MethodsThis prospective, multi-center, non-inferiority, randomized control trial（TARGETⅠ trial） was performed between August 2010 and April 2011, a total of 460 patients with primary, de novo, single vessel and single coronary lesion from 16 medical centers were enrolled. The diameter stenosis of target lesion was ≥70%, and lesion length was≤24 mm. The patients were randomly assigned to treatment with Firehawk stent （Firehawk stent group） or Xience V stent （Xience V stent group） groups by a web-based allocation system and was stratified by center. The late lumen loss after 9 months, target lesion failure （TLF） which was a composite of cardiac death, target vessel myocardial infarction, or ischemia driven target lesion revascularization, patient-oriented composite endpoint （PoCE） which was a composite of all cause death, all cause myocardial infarction, or any revascularization, and stent thrombosis after 5 years were compared between the two groups. Results（1） There were 2 patients without stent implantation dropped out of this trial. There were 227 patients in Firehawk stent group, and 231 patients in Xience V stent group. The baseline characteristics were similar between the two groups（all P〉0.05）. （2） The 9 months late lumen loss in Firehawk stent group was non-inferior to that in Xience V stent group （（0.13±0.24）mm vs. （0.13±0.18）mm, P=0.94）. （3） A total of 442 （96.5%） patients completed 5 years clinical follow-up. There were no significant differences on 5-year TLF rate （6.0%（13/217） vs. 6.7% （15/225）, P=0.77） and PoCE rate （12.0%（26/217） vs. 17.8% （40/225）, P=0.09） between the Firehawk stent group and Xience V stent group. （4） Kaplan-Meier analysis showed that TLF rates between 1-5 years were similar in Firehawk stent group and Xience V stent group （5.7% and 6.6% respectively, HR=0.88, 95%CI 0.42-1.84, P=0.72）. Land-Mark analysis showed that TLF rates bewteen 1-5 years were similar in Firehawk stent group and Xience V stent group （3.6% and 4.4% respectively, HR=0.83, 95%CI 0.34-2.00, P=0.67）. Kaplan-Meier analysis showed that PoCE rates between 1-5 years were also similar in Firehawk stent group and Xience V stent group （11.4% and 17.3% respectively, HR=0.64, 95%CI 0.39-1.04, P=0.07）. Land-Mark analysis showed that PoCE rates after 5 years were similar in Firehawk stent group and Xience V stent group （8.4% and 10.0% respectively, HR=0.66, 95%CI 0.40-1.10, P=0.11）. （5） No stent thrombosis was documented in Firehawk stent group during the 5 years follow-up period, and there was 1 case of stent thrombosis in Xience V stent group after 3 years of stent implantation. ConclusionTARGETⅠ trial results of 5 years follow up indicate the novel Firehawk stent have a durable safety and efficacy profile which is comparable to the Xience V stent in treating patients with single de novo coronary lesion. Clinical Trial Registration North American Clinical Trial Registration Center, NCT01196819.