摘要
目的及背景:冠状动脉长病变是指病变长度>20mm、ACC/AHA分型的C型病变。由于长病变自身的复杂性,既往采取长球囊扩张、长裸金属支架(BMS)置入或重叠BMS置入等治疗方式,不仅操作难度增加,远期过高的再狭窄发生率也造成其临床效果难以令人满意。近年来随着药物洗脱支架(DES)的临床应用日益广泛,诸多询证证据显示DES能显著降低远期再狭窄及靶血管或靶病变血运重建的发生率。因此,置入重叠DES逐渐成为目前临床上治疗冠状动脉长病变的主要手段之一。但重叠DES的应用也带来了一些新的问题,如重叠部位的延迟内皮化、晚期支架贴壁不良、支架断裂、晚期甚至极晚期支架内血栓及再狭窄等事件发生率的升高等,逐渐引起人们对重叠DES应用的忧虑。近年来问世并大规模临床应用的国产雷帕霉素可降解聚合物涂层药物支架(Excel,JW Medical)采用与以往雷帕霉素药物支架(SES)不同的血管壁侧单面可降解聚合物载药涂层技术,理论上可以避免目前临床使用的SES因为支架所有部位都被覆不可降解载药聚合物涂层导致的支架置入部位新生内膜增生过度和延迟内皮化等问题,从而实现预防再狭窄的同时避免晚期支架内血栓事件的发生。既往相关研究较多集中于单一Excel支架的临床应用,极少文献报道重叠Excel支架治疗冠状动脉长病变的临床效果。本研究目的即是通过对比置入重叠Excel支架和重叠Cypher支架患者术后住院期间和院外12个月临床随访期间主要心血管不良事件及支架内血栓事件的发生,及两者造影随访结果,评价置入重叠Excel支架治疗冠状动脉长病变的近期及远期的安全性及有效性,以及是否较置入重叠Cypher支架更具有优越性,并观察这两种雷帕霉素药物洗脱支架重叠置入后其重叠部位与非重叠部位造影结果的区别。
方法:回顾性选取2006年8月至2009年3月期间于武警总医院心内科行冠状动脉造影发现靶病变为冠状动脉长病变(病变长度>20mm),直径狭窄程度>75%或虽直径狭窄程度未及75%,但伴有严重心绞痛症状,靶病变重叠置入2枚直径在2.5mm～3.5mm间的Excel或Cypher(或Cypher Select)支架的稳定型心绞痛(SAP)及急性冠脉综合征(ACS)的新发冠状动脉(De-novo)病变的患者;排除存在严重并发症的急性心肌梗死、术中因非操作相关原因死亡、手术失败或靶病变置入直径<2.5mm或>3.5mm支架、既往曾实施靶病变或靶血管PCI或CABG、靶病变重叠置入>2枚支架、非Excel或Cypher支架或异种DES及住院期间非靶病变置入重叠支架患者。符合研究条件患者根据置入支架的不同分为Excel重叠组及Cypher重叠组,对其术后住院期间和院外12个月临床随访情况及术后6～12个月随访造影的影像学资料进行收集和分析,比较两组术后住院期间及院外12个月临床随访期间复合MACE、术后住院期间急性/亚急性支架内血栓事件及术后院外12个月临床随访期间晚期支架内血栓事件的发生情况,及造影随访再狭窄发生情况及晚期管腔丢失情况进行对比。影像学资料使用QAngio XA(Version 7.2,Medis)软件进行定量冠状动脉造影(Quantitative Coronary Angiography,QCA)分析。统计学处理:计量资料用均数±标准差(Mean±SD)表示,计数资料用百分比表示。计量资料事先进行正态分布及方差齐性检验,根据检验结果2组间比较采用成组t检验(Two-Samples t-Test)或Mann-Whitney U非参数检验,多组间比较采用方差分析(One-Way ANOVA法)或Kruskal-Wallis H非参数检验;计数资料2组间比较采用卡方检验(Pearsonχ2检验)或Fisher’s确切概率法,多组间比较采用卡方分割法。P<0.05(双侧)认为有统计学显著性差异。所有数据应用SPSS 13.0软件进行统计学检验与处理。
结果:于2006年8月至2009年3月期间在我院心内科行PCI时重叠置入支架患者657例,排除重叠置入>2枚支架患者66例、重叠置入2枚非Excel或Cypher支架患者113例、重叠置入异种DES患者52例、置入包括直径4.0mm的Excel支架患者12例、住院期间非靶病置入重叠支架患者37例及伴严重并发症的心肌梗死患者3例(其中2例术中死亡),共374例患者符合本研究入选条件。
根据置入的支架不同将患者分为Excel重叠组及Cypher重叠组,其中Excel重叠组211例(56.42%),Cypher重叠组163例(43.58%)。两组患者基线情况、临床特征及靶病变特征均无显著性差异;PCI操作过程中,除两组预扩张情况(94.8% vs. 98.8%,P=0.046)有所不同外,余无显著性差异;术前及术后即刻两组QCA分析得到的各项观察指标无显著性差异。
术后住院期间两组复合MACE发生率(5.7% vs. 6.1%,P=0.855)无显著性差异:两组死亡(2.4% vs. 2.5%,P=1.000),包括心源性死亡(1.9% vs. 2.5%,P=0.733)、心肌梗死(4.3% vs. 4.3%,P=0.989),包括非致死性心肌梗死(3.3% vs. 3.7%,P=0.849)、靶血管血运重建(0.9% vs. 1.8%,P=0.657),包括靶病变血运重建(0.9% vs. 1.8%,P=0.657)等事件发生率无显著性差异;两组ARC定义的急性∕亚急性血栓发生率(2.8% vs. 2.5%,P=1.000)无显著性差异。
术后院外12个月临床随访共纳入331例患者,失访率11.50%,其中Excel重叠组183例,Cypher重叠组148例患者。两组复合MACE发生率(6.6% vs. 8.8%,P=0.446)无显著性差异:两组死亡(2.2% vs. 2.0%,P=1.000)、包括心源性死亡(1.6% vs. 1.4%,P=1.000)、心肌梗死(2.2% vs. 2.0%,P=1.000)、包括非致死性心肌梗死(1.6% vs. 2.0%,P=1.000)、靶血管血运重建(4.9% vs. 6.1%,P=0.643)、包括靶病变血运重建(3.8% vs. 5.4%,P=0.492)等事件发生率无显著性差异;两组心绞痛复发率(31.1% vs. 32.4%,P=0.803)及因心绞痛再住院率(23.0% vs. 25.0%,P=0.664)无显著性差异;两组ARC定义的晚期支架内血栓发生率(2.7% vs. 2.7%,P=1.000)无显著性差异。
术后6～12个月内对167例患者进行了造影随访,随访率为44.65%,其中Excel重叠组84例,Cypher重叠组83例。两组造影随访距PCI天数(257.45±53.18 vs. 274.74±66.41)无显著性差异;两组支架内MLD、节段内MLD、近端支架边缘MLD、近端支架MLD、重叠部位MLD、远端支架MLD及远端支架边缘MLD均无显著性差异;两组节段内LLL及远端支架LLL无显著性差异,但支架内LLL(0.09±0.05 vs. 0.10±0.05,P=0.037)、近端支架边缘LLL(0.08±0.03 vs. 0.13±0.02,P<0.001)、近端支架LLL(0.11±0.03 vs. 0.14±0.02,P<0.001)、重叠部位LLL(0.16±0.02 vs. 0.20±0.02,P<0.001)及远端支架边缘LLL(0.06±0.02vs. 0.08±0.02,P<0.001)均有明显差异;两组支架内再狭窄率(6.0% vs. 9.6%,P=0.374)及节段内再狭窄率(9.5% vs. 12.0%,P=0.599)无显著性差异;Excel重叠组及Cypher重叠组各观察到1例动脉瘤形成,Excel重叠组中动脉瘤形成位于近端支架覆盖的血管壁范围内,Cypher重叠组中动脉瘤形成位于远端支架覆盖的血管壁范围内;两组在术后6～12个月造影随访中未观察到晚期支架内血栓形成。
除Excel重叠组组内近端支架边缘LLL与远端支架LLL相比无显著性差异外,两组组内近端支架边缘LLL、近端支架LLL、重叠部位LLL、远端支架LLL及远端支架边缘LLL间均有显著性差异(P<0.001);两组组内近端支架边缘、近端支架、重叠部位、远端支架及远端支架边缘各段再狭窄发生率间均无显著性差异。
结论: 1、置入重叠Excel支架治疗冠状动脉长病变,具有同重叠Cypher支架相似的良好的近期及远期临床安全性及有效性。2、置入重叠Excel支架较Cypher支架相比,能够有效减轻支架内晚期管腔丢失程度,可能与其血管壁侧单面可降解载药聚合物涂层的特性相关,在降低远期再狭窄发生率方面可能会优于Cypher支架。3、无论置入重叠Excel或Cypher支架,重叠部位的晚期管腔丢失较非重叠部位显著加重,但重叠部位再狭窄的发生率较非重叠部位无显著性差异。
Objective: Long coronary artery lesion that characterized of length more than 20mm, is type C lesion defined by AHA/ACC. Because of complication of long lesion, the method of dilatation by long balloon, long BMS implantation or overlapped BMSs implantation previously did not induce satisfactory clinical efficacy. With the utilization of DES more and more widespreadly, much evidence revealed that utilization of DES for treatment CAD could decrease the incidence of stent restenosis and TVR or TLR for long-term after PCI. Because of that, overlapped DES implantation has became one of the most important methods in treatment of long coronary artery lesion. But the DES overlapping brought about some new problems, such as delayed endothelialization, incomplete stent apposition, stents fracture, increasing incidence of late stent thrombosis or very late stent thrombosis, and stent restenosis, which induced more and more attention on it. Excel stent adopted new technology of single-sided biodegradable polymer-coated faced on the side of vessel wall which was different from other SES, and could avoid both SR or LST theoretically. More research were focused on clinical effects of single Excel stent previously, few literature concerning on clinical efficacy of overlapped Excel stents for treatment long coronary artery lesion. This study aims at evaluation on efficacy and safety of overlapped Excel stents implantation for treatment long coronary artery lesion by comparison the incidence of MACE, ST and SR after overlapped Excel or Cypher stents implantation during hospitalization and 12-month clinical follow-up, and observes the differences of angiographic results between overlapped site and non-overlapped site of these 2 kinds of SES.
Method: Consecutive patients with SAP or ACS who got long de-novo lesion of coronary artery and performed 2 overlapped Excel stents or Cypher stents implantation in cardiac and vascular department of General Hospital Of Chinese Army Police Force during 2006.8 to 2009.3 were enrolled in this study retrospectively; target lesion of which performed PCI with use of stents which diameter varied from 2.5mm to 3.5mm, and the diameter stenosis was more than 75%, or less than 75% but the patient ill with severe angina, were cured. Patients died but not caused by operation, patients with AMI which induced severe complication, patients who accepted unsuccessful PCI, patients who were cured with stent that diameter less than 2.5mm or more than 3.5mm, patients who were performed PCI or CABG on target lesion or target vessel previously, patients performed more than 2 stents, neither overlapped Excel stents nor Cypher stents, heterogeneous DES implantation or performed overlapped stents implantation for non-target lesion during hospitalization were excluded. Patients were divided into 2 groups by the type of stents implanted: the overlapped Excel stents group and the overlapped Cypher stents group. Information about hospitalization and 12-month clinical follow-up outside hospital after PCI and results of repeat CAG during the term of follow-up were collected and analyzed, the incidence of composite MACE and acute/subacute stent thrombosis during hospitalization, incidence of composite MACE and late stent thrombosis during 12-month clinical follow-up after PCI, and incidence of SR and LLL in repeat CAG during the term of follow-up between 2 groups were compared. Result of CAG before or after PCI and repeated CAG during the term of follow-up were performed QCA analysis by QAngio XA (Version 7.2, Medis) software.
Statistic analysis: Continuous variables are presented as Mean±SD, Categorical variables are presented as percentages. Normal distribution of all continuous variables was tested by Kolmogorov-Smirnov test first. Differences of continuous variables among 2 groups were analyzed by 2-samples t-test or nonparametric Mann-Whitney U test, differences of continuous variables among multi-groups were analyzed by One-Way ANOVA test or nonparametric Kruskal-Wallis H test; categorical variables were compared with Pearson chi-square test or Fisher’s exact test as appropriate between 2 groups. Differences with P value less than 0.05 (2-sided) were considered as statistical significance. All data were performed statistical analyses with use of SPSS software (Version 13.0 , SPSS).
Results: 657 consecutive patients performed overlapped DES were collected during 2006.8 to 2009.3, but 66 patients performed more than 2 stents implantation, 113 patients who were implanted neither overlapped Excel or Cypher stents, 52 patients who were performed heterogeneous DES implantation, 12 patients who were performed Excel stents implantation which diameter more than 4.0mm, 37 patients who were performed overlapped stents implantation in non-target lesion during hospitalization and 3 patients with AMI which induced severe complication (of 2 died during precedual) were excluded. 374 patients were enrolled in this study in all.
211 patients accepted 2 overlapped Excel implantation, and 163 patients accepted 2 overlapped Cypher implantation. The characteristics of baseline and target lesion, clinical characteristics between 2 groups are similar, information of PCI procedure reveal non-significant differences between 2 groups except the percentage of pre-dilatation (94.8% vs. 98.8%, P=0.046), the QCA data pre-procedure and post-procedure also reveal non-significant differences between 2 groups.
During hospitalization, between 2 groups, the incidence of composite MACE (5.7% vs. 6.1%, P=0.855) reveal non-significant differences: the incidence of death (2.4% vs. 2.5%, P=1.000), including cardiac death (1.9% vs. 2.5%, P=0.733), MI (4.3% vs. 4.3%, P=0.989), including immortal MI (3.3% vs. 3.7%, P=0.849), TVR (0.9% vs. 1.8%, P=0.657) and TLR (0.9% vs. 1.8%, P=0.657) reveal non-significant differences; the incidence of acute/subacute stent thrombosis defined by ARC (2.8% vs. 2.5%, P=1.000) also reveal non-significant differences.
331 patients (183 patients of Excel group and 146 patients of Cypher group) were followed-up during 12 months outside hospital after PCI. During this period, between 2 groups, the incidence of composite MACE (6.6% vs. 8.8%, P=0.446) reveal non-significant differences: the incidence of death (2.2% vs. 2.0%, P=1.000), cardiac death (1.6% vs. 1.4%, P=1.000), MI (2.2% vs. 2.0%, P=1.000), immortal MI (1.6% vs. 2.0%, P=1.000), TVR (4.9% vs. 6.1%, P=0.643) and TLR (3.8% vs. 5.4%, P=0.492) reveal non-significant differences; the reoccurrence of angina (31.1% vs. 32.4%, P=0.803) and admittion to hospital caused by angina (23.0% vs. 25.0%, P=0.664) are similar between 2 groups; the incidence of late stent thrombosis defined by ARC (2.7% vs. 2.7%, P=1.000) also reveal non-significant differences.
167 patients were performed repeat CAG (84 patients of Excel group and 83 patients of Cypher group) during 6~12 months after PCI. The results of CAG revealed that in-stent LLL (0.09±0.05 vs. 0.10±0.05, P=0.037), proximal edge LLL (0.08±0.03 vs. 0.13±0.02, P < 0.001), proximal stent LLL (0.11±0.03 vs. 0.14±0.02, P<0.001), overlapping site LLL (0.16±0.02 vs. 0.20±0.02, P<0.001), distal edge LLL (0.06±0.02 vs. 0.08±0.02, P<0.001) were different significantly, but the occurrence of in-stent restenosis (6.0% in Excel group and 9.6% in Cypher group, P=0.374) and in-segment restenosis (9.5% in Excel group and 12.0% in Cypher group, P=0.599) revealed non-significant differences between 2 groups. Aneurysm was observed in 2 patients during follow-up of angiography, the one was in proximal stent in Excel group, the other was in distal stent in Cypher group. No late stent thrombosis was observed in angiography of follow-up.
The LLL measurements of proximal edge, proximal stent, overlapping site, distal stent and distal edge either in Excel group or Cypher group revealed significant differences between each other (except difference between LLL of proximal edge and distal stent in Excel group). The incidence of restenosis of proximal edge, proximal stent, overlapping site, distal stent and distal edge in either Excel group or Cypher group revealed non-significant differences between each other.
Conclusions: 1. The safty and efficacy of overlapped Excel stents implantation to treat long coronary lesion is similar to Cypher stents. 2. The degree of late lumen loss in-stent caused by stents implantation could be relieved by using overlapped Excel stent than Cypher stents for the technology that single-sided biodegradable polymer-coated faced on the side of vessel wall of Excel stent, so application of overlapped Excel stents may reduce the possibility of SR for long time than Cypher stents. 3. The LLL of overlapped site is more severe than other regions, whatever overlapped Excel stents or Cypher stents implantation, but the incidence of restenosis in overlapped site are not higher than other regions significantly.
引文
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4 Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. Eng J Med, 2002, 346:1773-1780
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6 Schampaert E, Cohen EA, Schlüter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de-novo lesions in small native coronary arteries (C-SIRIUS) . J Am Coll Cardiol, 2004, 43: 1110-1115
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