Excel^(TM)支架治疗冠状动脉小血管病变的长期临床安全性与有效性研究

Long-term clinical safety and efficacy of Excel^(TM) stent in treating small vessel coronary artery disease:a subgroup analysis of the CREATE study

目的评估国产生物可降解涂层雷帕霉素洗脱支架(ExcelTM,山东吉威医疗制品有限公司)治疗冠状动脉小血管病变的长期临床安全性与有效性。方法 2006年6月至11月在4个国家(中国、印度尼西亚、马来西亚、泰国)的59个中心共有2077例接受单一ExcelTM支架治疗的患者连续入选CREATE研究。以靶病变两端参考血管直径≤2.75mm作为小血管标准(有一支靶血管直径≤2.75mm即为小血管病变患者),将患者分为小血管病变组(886例,42.7%)和非小血管病变组(1191例,57.3%)。术后接受双联抗血小板药物(氯吡格雷和阿司匹林)治疗6个月,随后单用阿司匹林长期治疗,比较两组术后9个月定量冠状动脉造影(quantitive coronary angiography,QCA)复查结果及18个月临床随访主要不良心脏事件(major adverse cardiac events,MACE)、心性死亡和血栓事件的发生率。结果与非小血管组相比,小血管组女性(29.0%比24.5%)、高血压(59.9%比52.6%)、糖尿病(23.4%比19.6%)、既往有心肌梗死(14.0%比9.2%)的患者较多,平均年龄(61.9±10.6)岁比(59.6±11.4)岁。氯吡格雷用药时间两组(200.1±55.0)d比(197.4±55.0)d。小血管组患者病变较长(23.23±14.14)mm比(21.43±11.79)mm,人均支架置入数多(2.23±1.33)枚比(1.49±0.82)枚。术后9个月QCA结果显示,小血管组和非小血管组支架内晚期管腔丢失(0.20±0.38)mm比(0.21±0.42)mm和再狭窄率(3.9%比3.4%)。在合并有直径>2.75mm的非小血管病变的小血管组患者中,小血管和非小血管支架内晚期管腔丢失(0.23±0.40)mm比(0.31±0.60)mm和再狭窄率(4.4%比8.4%)。18个月临床随访结果表明,小血管组靶病变血运重建率(2.8%比1.2%)高于非小血管组,但两组MACE(3.9%比2.5%)、心性死亡(0.9%比1.3%)和支架内血栓(1.0%比0.8%)发生率。多因素Cox回归分析结果表明,小血管病变并非ExcelTM支架置入术后MACE发生的独立危险预测因素(OR=0.848,95%CI0.482~1.491,P=0.567)。结论 ExcelTM支架治疗冠状动脉小血管病变的长期疗效及安全性与非小血管病变相近,但还需随机对照临床研究进一步加以证实。

Objective To evaluate the long-term clinical safety and efficacy of a biodegradable polymer-coated sirolimus-eluting stent （ExeelTM, JW Medical System, Weihai, Shandong） in treating patients with small vessel coronary artery disease. Methods Between June and November 2006, a total of 2077 patients who exclusively treated with ExcelTM stents were enrolled in the CREATE study at 59 centers from 4 countries. The small vessel disease .was defined as at least one target vessel with reference vessel diameter of less than 2. 75 mm. The patients were divided into small vessel group （ n = 886, 42. 7% ） and non-small vessel group （n= 1191, 57.3% ） according to the definition. Recommended anti-platelet regimen included clopidogrel and aspirin for 6 months followed by chronic aspirin therapy. Quantitive coronary angiographic （QCA） results at 9 months and clinical outcomes including major adverse cardiac events （MACE）, cardiac death and stent thrombosis at 18 months were evaluated. Results Compared with the patients in non-small vessel group, patients in small vessel group were more older （61.9 -＋ 10. 6 years vs. 59.6 ± 11.4 years, P 〈 0. 001 ） and had higher proportions of female （ 29.0% vs. 24. 5% , P -=-0. 022 ） , hypertension （59. 9% vs. 52. 6% , P = 0. 001 ） and prior myocardial infarction （ 14. 0% vs. 9. 2% , P = 0. 001 ）. There were no differences in the average duration of clopidogrel treatment between the two groups （200. 1±55.0 days vs. 197.4 ±55.0 days, P =0. 262）. Patients in small vessel group had longer average lesion length （23.23 ±14. 14 mm vs. 21.43±11.79 ram, P = 0. 039） and larger number of stents per patient （2. 23± 1.33 vs. 1. 49± 0. 82, P 〈 0. 001 ）. Follow-up QCA results showed that there was no significant differences in late lumen loss （ 0. 20± 0. 38 mm vs. 0. 21 ± 0.42 ram, P = 0. 654 ） and in-stent restenosis （3.9% vs. 3.4%, P =0. 856） between the two groups at 9 months. In patients with both small vessel lesions and non-small vessel lesions （defined as reference vessel diameter more than 2.75ram） , there was no significant differences in late lumen loss （0.23±0. 40 mm vs. 0. 31±0. 60 ram, P =0. 181 ） and instent restenosis （4. 4% vs. 8.4% , P =0. 225） between the two groups at 9 months. Clinical outcomes at 18 months showed the target lesion revascularization rate in small vessel group was higher than that in non-small vessel group （2. 8% vs. 1.2%, P =0.006）. However, there were no significant differences in MACE （3. 9% vs. 2. 5%, P=0.086）, cardiac death （0.9% vs. 1.3%, P=0.441） and stent thrombosis （ 1.0% vs. 0. 8% , P = 0. 528 ） between the two groups. Cox Multivariate regression analysis showed the vessel size was not an independent predictor of MACE after ExcelTM stent implantation （ OR O. 848, 95% CI 0. 482 - 1. 491, P =0. 567）. Conclusions Long-term clinical safety and efficacy of ExcelTM biodegradable polymer-coated sirolimus-eluting stent for treatment of small vessel coronary artery disease are same as those for non-small vessel disease. These conclusions need further confirmation by randomized controlled clinical studies.