新型生物可降解涂层靶向释放雷帕霉素支架治疗中等复杂冠状动脉病变的长期安全性和有效性：TARGETⅡ研究5年随访结果

Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of de novo coronary lesions： 5-year results of the TARGET Ⅱ trial

目的评价生物可降解涂层钴铬合金雷帕霉素洗脱支架FIREHAWK治疗中等复杂冠状动脉病变（包括小血管病变、长病变和多支病变）的长期安全性和有效性，并探讨SYNTAX评分对其长期预后的预测价值。方法TARGET Ⅱ研究是一项前瞻性、多中心、单臂临床研究。国内24个医学中心参与，2011年8月至2012年2月期间共入选新发冠状动脉（冠脉）病变患者730例，全部接受FIREHAWK支架治疗。收集患者一般临床资料（包括糖尿病、小血管病变、长病变以及多支病变）。主要终点为靶病变失败（TLF）作为器械源性复合终点，包括心原性死亡、靶血管心肌梗死（TV-MI）及缺血驱动的靶病变血运重建（TLR）。次要终点，其一为患者源性复合终点，包括全因死亡、心肌梗死、随访期再次血运重建；另一个为美国和欧洲学者组成的学术研究联盟（ARC）定义的确定或可能的支架内血栓（包括早期、晚期和极晚期）。对参考血管直径≥1.5 mm的血管中每个〉50%狭窄的病变均进行SYNTAX评分，≤7分为低分、〉7分且≤12分为中分、〉12分为高分。临床随访直至术后5年。采用多因素Cox回归分析不同因素对主要终点的影响。结果本研究共入选患者730例，SYNTAX评分（10.9±6.9）分，完成5年随访的患者683例（93.6%）。发生TLF 58例（8.5%），包括心原性死亡14例（2.0%）、靶血管相关心肌梗死30例（4.4%）、缺血驱动的靶病变血运重建23例（3.4%）。发生患者源性复合终点112例（16.4%），确定或可能的支架内血栓5例（0.7%）。多因素Cox回归分析结果显示糖尿病（HR=1.123,95%CI 0.623~2.026,P=0.699）、小血管病变（HR=0.909,95%CI 0.526~1.570,P=0.732）、长病变（HR=1.561,95%CI 0.922~2.640,P=0.097）以及多支病变（HR=1.062, 95%CI 0.611~1.846,P=0.830）不增加TLF风险，且SYNTAX评分高不增加TLF风险（中分比低分HR=1.203，95%CI 0.607~2.385，P=0.597；高分比低分HR=1.548，95%CI 0.829~2.892，P=0.171）。结论新型生物可降解涂层的FIREHAWK支架，对于中等复杂冠状动脉病变患者的长期安全性和有效性较好。SYNTAX评分对于FIREHAWK支架术后TLF预测价值有限。临床试验注册号Clinical Trial.gov，NCT0141264。

ObjectiveThis study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent （SES） in patients with moderate-complex coronary lesions （including patients with small vessel disease, long lesion and multi vessel disease）, and to validate the ability of the SYNTAX score （SS） to predict clinical outcomes in patients treated with FIREHAWK stent. MethodsTARGETⅡ was a prospective, multicenter, single-arm clinical trial, a total of 730 patients who underwent percutaneous coronary intervention （PCI） of de novo lesions in native coronary arteries in 24 medical centers in China from August 2011 to February 2012 were enrolled in this study. All patients were exclusively treated with the FIREHAWK stent. Clinical data including patients with diabetes, small vessel disease, long lesion and multi vessel disease were analyzed. The primary composite endpoint was the target lesion failure （TLF） of cardiac death, target vessel-related myocardial infarction （TV-MI）, or target lesion revascularization （TLR）. The secondary composite endpoint was patient-oriented endpoint （PoCE）, a composite of all death, all myocardial in farction （MI）, or any repeat revascularization; definite/probable stent thrombosis （ST） （including acute, late, and very late thrombosis） . SS was calculated in lesions with stenosis more than 50% with coronary artery diameter greater than 1.5 mm. Patients were grouped by tertiles of SS （≤7, 〉7 to ≤12, 〉12）. Follow-up was performed up to 5 years. ResultsA total of 730 patients were enrolled in the TARGET Ⅱ trial. The average SS was 10.9±6.9. 683 （93.6%） patients completed 5-year clinical follow-up. The 5-year incidence of TLF was 8.5%（58/683）. The incidence of TLF components was as follows： cardiac death 2.0%（14/683）, TV-MI 4.4%（30/683）, TLR 3.4%（23/683）. The incidence of PoCE was 16.4%（112/683）. The incidence of definite/probable stent thrombosis was 0.7%（5/683）.Multivariable Cox regression analysis showed that the diabetes subgroup （HR=1.123, 95%CI 0.623-2.026, P=0.699）, the small vessel disease subgroup （HR=0.909, 95%CI 0.526-1.570, P=0.732）, the long lesion subgroup （HR=1.561, 95%CI 0.922-2.640, P=0.097）, and the multi vessel disease subgroup （HR=1.062, 95%CI 0.611-1.846, P=0.830） did not increase the HR of TLF compared with the counterpart subgroups. Multivariable Cox regression analysis showed that the hazard of TLF was not increased in the middle and high SS groups as compared with the low SS group （HR=1.203,95%CI 0.607-2.385,P=0.597;HR=1.548,95%CI 0.829-2.892,P=0.171）. ConclusionsThe 5 years follow-up results of TARGET Ⅱ trial shows that the biodegradable polymer of FIREHAWK stents have long-lasting safety and efficacy for patients with moderate-complex coronary lesions. SS is not the predicting factor for the occurrence of TLF in FIREHAWK treated patients with moderate-complex coronary lesions. Trial Registration Clinical Trials.gov, NCT0141264.