国产可降解雷帕霉素药物洗脱支架置入的疗效评价：与金属裸支架比较

背景：药物洗脱支架明显降低了再狭窄率,但永久聚合物涂层在抑制血管平滑肌细胞增生的同时,阻碍血管完全内皮化进程,促使再狭窄发生,且永久聚合物涂层可引发晚期血栓等并发症。目的：观察冠心病合并糖尿患者置入国产可降解药物洗脱支架后的远期疗效和安全性,并与置入金属裸支架患者进行比较。方法：实验组选择冠心病合并2型糖尿病患者136例,首次经皮冠状动脉成形治疗,置入国产可降解药物洗脱支架（EXCELTM）,并以同期行金属裸支架置入治疗的冠心病合并2型糖尿病患者87例为对照组,随访12个月以上,记录主要不良心血管事件发生情况,并复查冠状动脉造影。结果与结论：实验组129例,对照组83例完成（13.5±3.5）个月随访,实验组及对照组分别有8例及12例患者发生不良心血管事件,两组间差异有显著性意义（P=0.045）,对照组靶血管血运重建及再发心绞痛多于实验组（P〈0.05）。两组患者随访冠状动脉造影的定量分析提示实验组最终丢失指数小于对照组（P〈0.05）,再狭窄率低于对照组（P〈0.05）。说明对于冠心病合并糖尿病患者,应用国产可降解药物洗脱支架可降低不良心血管事件发生率,减少再狭窄,改善患者远期预后,安全性能良好。     

合并2型糖尿病的冠状动脉小血管病变植入雷帕酶素洗脱支架与金属裸支架疗效比较

目的评价真实临床环境下合并2型糖尿病的冠状动脉小血管(直径≤2.5mm)植入雷帕酶素洗脱支架(SES)与金属裸支架(BMS)的不同疗效。方法选择接受SES支架(78例)/BMS支架(72例)治疗同时合并2型糖尿病的冠状动脉小血管病变患者;比较2组患者临床特征、冠状动脉造影病变特点、支架植入术相关参数、住院期间及术后临床、冠状动脉造影随访结果,采用多元逻辑回归方法评价患者术后再狭窄发生的影响因素。结果①接受SES治疗78例(101处病变),接受BMS治疗72例(92处病变);2组仅1/5左右的患者在入院时血糖控制达标;②SES组平均植入支架长度>BMS组(26.41mm比22.12mm,P<0.05);③所有患者均接受了临床随访,平均随访(7.56±1.53)个月,有92.3%患者接受了冠状动脉造影随访。SES组在再发心绞痛、心肌梗死方面低于BMS组(P<0.01),但2组远期病死率差异无显著性(P>0.05)。SES组造影再狭窄发生率显著低于BMS组(17.1%比31.0%,P<0.01);④多元逻辑回归分析结果显示分叉病变、串联支架植入是合并2型糖尿病的冠状动脉小血管患者SES植入后发生再狭窄的独立预测因素,OR值分别为1.91(95%CI0.37~3.82,P<0.05)、1.12(95%CI0.31~3.13,P<0.05)。结论真实临床环境下,合并2型糖尿病的冠状动脉小血管(直径≤2.5mm)植入SES疗效优于BMS。     

国产与进口雷帕霉素洗脱支架在冠状动脉粥样硬化性心脏病中的疗效比较

目的:比较国产雷帕霉素药物洗脱支架(Firebird 2)和进口雷帕霉素药物洗脱支架(Cypher Select)在冠状动脉粥样硬化性心脏病(冠心病)患者经皮冠状动脉介入术中的临床疗效。方法:选择2010年5月—2011年12月在上海市第六人民医院心内科采用雷帕霉素药物洗脱支架治疗的冠心病患者。根据植入支架种类分为Firebird 2组和Cypher组。随访时间25~40个月,平均(32.54±3.90)个月,其中Firebird 2组完成随访139例,Cypher组完成随访125例。比较两组患者随访期间主要心血管不良事件(MACE,包括心源性死亡、非致死性心肌梗死、靶血管再次血运重建)以及支架内再狭窄、确定的支架内血栓发生情况。结果:Firebird 2组男性患者比例低于Cypher组(P0.05)。Firebird 2组患者血浆N末端B型钠尿肽前体(NTproBNP)含量、靶病变长度、每处病变植入支架数大于Cypher组(P0.05)。Firebird 2组患者和Cypher组患者在心源性死亡(4.3%vs 3.2%)、非致死性心肌梗死(1.4%vs 1.6%)、靶血管再次血运重建(4.3%vs 5.6%)、MACE(9.4%vs 8.8%)方面差异均无统计学意义。Firebird 2组患者和Cypher组患者支架内再狭窄、确定的支架内血栓发生差异亦无统计学意义。Logistic回归分析显示:年龄(OR=1.11,95%CI 1.05~1.18,P=0.000)、糖尿病(OR=2.70,95%CI 1.02~7.15,P=0.045)是随访期间MACE发生的独立危险因素;支架种类(OR=0.88,95%CI 0.34~2.24,P=0.782)不是MACE发生的独立危险因素。结论:Firebird 2雷帕霉素药物洗脱支架和Cypher雷帕霉素药物洗脱支架在冠心病治疗中的长期临床疗效及安全性基本类似。     

Excel雷帕霉素药物洗脱支架的临床应用

目的观察应用Excel雷帕霉素药物洗脱支架的近期疗效及安全性。方法选择2005年1月～2006年12月89例接受药物涂层支架的患者。39例患者植入Cypher支架60个。50例患者植入Excel支架83个，观察Excel支架的近期疗效及安全性。结果两组基本临床特征相似，狭窄程度及病变范围相似，93％的病人完成6个月随访，两组病人均未发生死亡、ST段抬高性心肌梗死，6个月内因胸痛再入院者，Cypher支架组2例，Excel支架组3例，复查造影，均未需再次血管重建术。结论国产Excel雷帕霉素药物洗脱支架临床应用安全，近期主要心血管事件与Cypher药物洗脱支架相似。     

药物洗脱支架与裸支架临床应用的安全性比较

目的:评价药物洗脱支架与裸支架临床应用中的安全性,观察药物洗脱支架与裸支架在冠状动脉粥样硬化性心脏病治疗中的应用.方法:以计算机检索方法在检索中国期刊全文数据库中(CNKI:2004/2008)检索关于药物洗脱支架与裸支架的临床研究与实验研究的随机对照实验,检索词为"洗脱支架、裸支架".检索后对每项研究的资料结果进行提取、分析.结果:共有19项实验2 731例血管内支架置入患者符合纳入标准,药物洗脱支架与裸支架置入后比较,应用药物洗脱支架血管再狭窄率均较术前降低,随访结果显示药物洗脱支架较金属裸支架能明显减低再狭窄率,靶病变血管重建率等,但其远期在体内对血流动力学的影响尚有待进一步随访观察.结论:与金属裸支架相比,药物洗脱支架在小血管复杂病变中置入是有效的,且能明显减少术后再狭窄和靶病变血运重建率.但由于纳入试验少,证据的强度不足,其他有效性指标和安全性,有待更多证据加以评价.     

国产雷帕霉素药物洗脱支架治疗冠心病的早期疗效

经皮冠状动脉介入治疗(PCI)是冠心病治疗的一个里程碑,防治术后再狭窄一直是刻领域最重大的难题.     

可降解与非可降解药物洗脱支架生物相容性的差异比较

目的:探讨非可降解药物洗脱支架置入后存在的问题,研究可降解支架的生物相容性.方法:以"可降解,药物洗脱支架,相容性"为检索词,检索中国期刊全文数据库(1999-01/2009-06);以"degradable.drug-eluting stent,compatibility"为检索词,检索PubMed数据库(1999-01/2009-06),文献检索语种限制为中文和英文.以支架的生物相容性,冠状动脉内皮化的程度和支架内再狭窄的发生率为评价指标.纳入可降解药物洗脱支架相关的文献;排除研究其他类型支架的文献.结果:计算机初检得到236篇文献,根据纳入排除标准,对33篇文献进行分析.现今药物支架的载体材料大都是不可降解的聚合物材料,经过长时间的人体腐蚀,材料本身会老化、脱落,就会在血管组织内形成小块,从而可能引起晚期的不良反应.而如果采用生物可降解的材料作为药物载体材料,那么就有可能减少晚期不良反应的出现.生物可降解支架,既可暂时支撑管壁,保持血管通畅,又能抑制早期血栓形成及晚期新生内膜增生,还可作为药物局部投放的载体,达到有效防止支架置入后血管急性闭塞和降低再狭窄发生率.结论:相对于不可降解药物洗脱支架,可降解药物洗脱支架具有良好的生物相容性和广阔的应用前景.     

EXCEL雷帕霉素药物洗脱支架临床疗效及观察体会

目的评价国产EXCEL雷帕霉素药物洗脱支架临床疗效。方法90例冠心病患者分3组,分别植入EX-CEL药物洗脱支架、Cypher药物洗脱支架及普通金属支架共计195枚,观察了3组支架的安全性及临床近期疗效。结果3组狭窄程度及病变长度无明显差别,分别经(12.9±2.1)atm、(13.4±3.3)atm、(13.0±4.2)atm扩张支架膨胀完全,均可完成对吻扩张,总的植入成功率为99.5%。与普通支架相比,使用EXCEL及Cypher药物洗脱支架组患者年龄大,合并高血压等心血管疾病数多(均为P<0.05)。使用EXCEL支架组3支病变也明显多于Cypher及普通支架组(P<0.05)。75例患者随访超过3个月(随访率为83.3%),普通支架组1例猝死,MACE发生率为2.7%,心绞痛复发4例;两种药物洗脱支架随访无1例发生MACE,心绞痛复发5例。结论国产EXCEL雷帕霉素药物洗脱支架临床应用安全,近期疗效与Cypher药物洗脱支架相近,PC I后近期主要不良心脏事件的发生率明显低于普通金属支架。     

药物洗脱支架与金属支架生物相容性比较及支架置入后的血管再狭窄

药物洗脱支架与裸金属支架相比,最大的改进就是在原有裸金属支架平台上,增加了药物载体和药物.虽然冠状动脉支架的成功率和安全性有了提高,但是再狭窄仍然足限制支架应用的一个障碍.药物洗脱支架置入后的过敏反应已有报道.文章在药物洗脱支架与普通金属裸支架的生物相容性比较分析的基础上,对药物洗脱支架置入后的再狭窄进行了临床研究,探讨了支架再狭窄产生的原因并从临床实例角度综合研究了药物洗脱支架置入后再狭窄的新进展与启示.     

国产与进口雷帕霉素洗脱支架的临床应用研究

目的比较国产雷帕霉素洗脱支架(Firebird,微创公司)与进口雷帕霉素洗脱支架(Cypher,Johnson&Johnson公司)临床应用的安全性及近、远期疗效。方法接受国产与进口雷帕霉素洗脱支架治疗的冠心病患者共84例,其中Firebird支架组31例(植入支架38个),Cypher支架组53例(植入支架80个)。观察术中两组患者介入技术指标及住院和(或)门诊随访6个月期间临床主要不良心血管事件(MACE)的发生率。结果两组手术均成功,住院期间及术后6个月随访MACE的发生率类似。Firebird支架组与Cypher支架组在冠状动脉病变的类型(A、B、C型)、病变累及的血管数、病变累及的部位、平均支架管径、直接支架术的使用率、Crush技术的应用方面差异无统计学意义,但在Firebird支架组支架使用数较Cypher支架组少[(1.23±0.43)个vs(1.51±0.74)个,P=0.03]、植入支架的总长度在Firebird支架组较Cypher支架组短[(28.13±11.57)mm vs(36.38±19.18)mm,P=0.02]、在靶血管直径狭窄程度上Cypher支架组明显较Fire-bird支架组严重[(91.89±5.64)%vs(87.73±7.07)%,P=0.004]。结论Firebird支架与Cypher支架在植入技术以及临床近、远期疗效方面无差异。     

Off-label use of stents: bare-metal versus drug-eluting stents

Drug-eluting stents (DES) became the default strategy for percutaneous revascularization due to their improved intermediate-term outcomes when compared with bare-metal stents (BMS) in the pivotal randomized, controlled trials. The excellent results of DES in on-label or US FDA-approved indications led to extrapolation of the results to more complex situations that were excluded from initial pivotal trials; such as off-label indications. Safety concerns began to grow after reports of increased late thrombosis and possibly associated increased death and myocardial infarction with DES, especially in the off-label situations. Recently, however, several important published registries have calmed some of those uncertainties and reassured the cardiology community of the safety and efficacy of DES compared with BMS. There is an overall poorer outcome with off-label use of any stent (BMS or DES) compared with standard or on-label use. This difference in outcome is most likely related to patient or specific coronary lesion characteristics or comorbidities that predispose an individual to adverse outcomes regardless of the stent type used. It is accepted now that DES use does result in a small increased risk of late thrombosis, but that risk is offset by a significant reduction in restenosis. Overall, the current data suggest that the use of DES in most lesion subsets is at least as safe as and clearly more efficacious than use of BMS in similar situations.     

Off-label use of stents: bare-metal versus drug-eluting stents

Drug-eluting stents (DES) became the default strategy for percutaneous revascularization due to their improved intermediate-term outcomes when compared with bare-metal stents (BMS) in the pivotal randomized, controlled trials. The excellent results of DES in on-label or US FDA-approved indications led to extrapolation of the results to more complex situations that were excluded from initial pivotal trials; such as off-label indications. Safety concerns began to grow after reports of increased late thrombosis and possibly associated increased death and myocardial infarction with DES, especially in the off-label situations. Recently, however, several important published registries have calmed some of those uncertainties and reassured the cardiology community of the safety and efficacy of DES compared with BMS. There is an overall poorer outcome with off-label use of any stent (BMS or DES) compared with standard or on-label use. This difference in outcome is most likely related to patient or specific coronary lesion characteristics or comorbidities that predispose an individual to adverse outcomes regardless of the stent type used. It is accepted now that DES use does result in a small increased risk of late thrombosis, but that risk is offset by a significant reduction in restenosis. Overall, the current data suggest that the use of DES in most lesion subsets is at least as safe as and clearly more efficacious than use of BMS in similar situations.     

雷帕霉素药物洗脱支架置入后发生血管再狭窄的相关因素及其安全性

目的:评价雷帕霉素药物洗脱支架置入的安全性,分析雷帕霉素药物洗脱支架支架血栓发生率和特征,探讨雷帕霉素药物洗脱支架治疗的患者中造影证实的支架血栓事件风险.方法:以计算机检索方法在检索中国期刊全文数据库中(CNKI:1997/2009)检索关于雷帕霉素药物洗脱支架血栓形成原因分析及安全性的自身前后对照实验,检索词为"雷帕霉素、药物洗脱支架、金属裸支架、支架内血栓".检索后对每项研究的资料结果进行提取、分析.结果:共有12项实验3 839例雷帕霉素药物洗脱支架置入患者符合纳入标准,雷帕霉素药物洗脱支架置入后血管脉狭窄率均较术前降低,随访结果显示国产雷帕霉素洗脱支架与金属裸支架内血栓的发生率均较低,两者无显著性差异,再狭窄率国产雷帕霉素洗脱支架支架明显低于金属裸支架.远期临床随访结果表明,延长联合抗血小板治疗时间很有必要.结论:雷帕霉素洗脱支架置入后的安全性尤其是晚期血栓问题的确值得关注,但发生率很低,临床实践中需要对雷帕霉素洗脱支架安全性以及危险与获益的相关性进行合理的判断.治疗多支血管病变时全部采用雷帕霉素洗脱支架优于金属裸支架,可获得较高的收益与风险比.     

The average stent length is longer and the average stent diameter is shorter in patients with drug-eluting stents versus bare-metal stents during percutaneous coronary intervention

Drug-eluting stents (DES) were inserted in 180 patients (270 stents), mean age 63 years, and bare-metal stents (BMS) were inserted in 191 patients (301 stents), mean age 63 years, during percutaneous coronary intervention. Baseline characteristics were similar for patients treated with DES or BMS. The average stent length was longer for DES (16.83 mm) versus BMS (15.45 mm) (P = 0.0026). The average stent diameter was shorter for DES (2.89 mm) versus BMS (3.00 mm) (P = 0.00027). In-hospital stent thrombosis occurred in one of 270 DES (0.4%) versus three3 of 301 BMS (1.0%) (P = not significant).     

生物可降解性血管内支架及药物释放支架的研制

目的探讨采用溶液中加入药物的方法制作雷帕霉素释放BES的可行性及载药量准确性;明确裸BES、雷帕霉素释放BES及ASODN涂层BES与金属支架在力学性能方面的差异。方法应用高分子材料PLLA制作生物可降解血管内支架;采用溶液中加入药物的方法制作生物可降解雷帕霉素释放支架;采用表面涂层方法制作生物可降解反义寡核苷酸涂层支架。应用HPLC法对雷帕霉素释放BES的载药量进行检测。对三种支架进行径向支撑力测试并与金属支架比较。结果制作出BES基杆直径为0.5mm,扩张后直径为4.5或5.0mm,长度均为15mm。三种BES外观无明显区别;雷帕霉素释放BES平均载药量为181.4μg,与支架制作过程中的设计载药量基本一致;支撑力测试结果表明:三种PLLA支架径向支撑力略低于金属支架;裸BES与涂层BES径向支撑力相似,略高于雷帕霉素BES。结论生物可降解材料PL-LA制作的裸支架、载药支架及涂层支架的径向支撑力均略低于金属支架,载药支架径向支撑力略低于裸支架及表面涂层支架。溶液中加入雷帕霉素的方法含量可靠,可以代替支架表面多孔构型的加工工艺。     

Long-term outcome after drug-eluting stent implantation in comparison with bare metal stents: a single centre experience

Background  

The aim of our study was to evaluate the effect of drug-eluting stents (DES) compared with bare-metal stents (BMS) on all-cause mortality and target vessel revascularization (TVR) in a “real-world” clinical setting.     

Development of biodegradable zein-based bilayer coatings for drug-eluting stents

Drug-eluting stents (DES) have been widely used for the treatment of cardiovascular diseases. Nevertheless, chronic inflammation and delayed re-endothelialization still represent challenges for their clinical use. In the present work, we developed novel bilayer coatings for stent applications that could overcome these limitations, exclusively using biodegradable plant-based drugs and polymers. In particular, stainless steel surfaces were coated with rutin-loaded zein (the active layer) and cross-linked alginate (the sacrificial layer) via facile dip and spray coating methods. Various mechanical tests and analysis tools, such as infrared spectroscopy, water contact angle measurements, and scanning electron microscopy were used to characterize the coated surfaces. Degradation and release studies of the films were extensively carried out and compared. The release rate of rutin from the bilayer coating reached 66.1 ± 3.2% within 24 hours of incubation (initial burst period), while the rest of the drug was released over 21 days in a sustained manner. Antioxidant assays confirmed that rutin retained its free radical scavenging ability after being eluted in phosphate buffer at 37 °C. In vitro results with human fibroblasts and endothelial cells suggested that the coating materials and their degradation products are highly biocompatible. In conclusion, our novel drug-eluting coatings, fabricated with natural biodegradable polymers, are promising materials for DES applications, allowing a sustained drug delivery and improving the biocompatibility of cardiovascular implanted devices.

Zein-based biodegradable bilayer coatings were successfully prepared and characterized. Release profiles, antioxidant potential, and biocompatibility were investigated, aiming for more sustainable coatings for drug-eluting stents.     

药物洗脱支架置入术后非急性血栓预防的临床研究

目的 探讨药物洗脱支架(DES)置入术后非急性血栓的防治,以减少DES置入术后急性心肌梗死(AMI)等事件的发生.方法 选择2005年1月到2008年9月在本院置入DES的手术患者,按入院顺序随机将患者分为两组进行不同方案的抗血栓治疗.对照组患者术后应用阿司匹林联合氯吡格雷抗血小板治疗(双抗治疗);试验组患者术后在双抗治疗基础上应用替罗非班和华法林,华法林疗程为6个月,将国际标准化比值(INR)维持在1.5 ～ 2.0.两组患者术后1～3个月随访1次,至2012年10月为止.按照美国学术联合会对支架血栓的定义判定支架血栓形成,主要终点指标为主要不良心脑血管事件(MACCE),次要终点指标为出血及不良反应.结果 共入选505例患者,试验组245例,对照组260例.试验组术后1 ～ 48个月MACCE均显著低于对照组(1个月:0.41％比3.08％,2～6个月:0比2.31％,7～12个月:0.82％比4.23％,13～24个月:1.22％比8.85％,25 ～ 48个月:2.04％比12.31％,均P＜0.05),其中试验组心源性死亡(13 ～24个月:0.41％比3.08％,25～48个月:0.82％比4.23％)、与靶血管无关的非致死性AMI(25 ～ 48个月:0.41％比3.08％)、靶血管的血运重建(13 ～ 24个月:0.41％比3.08％,25～48个月:0.82％比4.23％)均较对照组明显减少(均P＜0.05).试验组术后亚急性支架血栓形成、晚期支架血栓形成、极晚期支架血栓形成的发生率显著低于对照组(0比2.31％,0.82％比4.23％,1.63％比8.46％,均P＜0.05).试验组轻微出血发生率略高于对照组(3.27％比1.54％,P=0.167),无严重出血发生.全部患者也无其他严重不良反应发生.结论 DES置入术后在应用阿司匹林和氯吡格雷双抗治疗基础上,联合替罗非班及华法林,可预防支架血栓形成,降低MACCE和严重出血的发生率.     

冠状动脉内药物洗脱支架或金属裸支架置入对患者血小板功能的影响

背景:冠状动脉内置入药物洗脱支架可以显著降低冠状动脉介入治疗后再狭窄的发生率和主要心血管不良事件,提高患者的生活质量,在临床得到了广泛应用.但近期的多项荟萃分析说明,与金属裸支架相比,药物洗脱支架显著增加晚期支架血栓形成,增加全因性死亡率.目的:观察冠状动脉支架置入前、后和随访6个月血小板膜糖蛋白的变化,对比分析短、中期内置入药物洗脱支架或金属裸支架对血小板活化影响的差异.方法:对2007-06/2009-06因急性冠脉综合征成功进行冠状动脉内支架置入治疗的104例患者进行回顾性分析,其中使用药物洗脱支架68例,金属裸支架36例.同时纳入34例因疑诊急性冠脉综合征而进行造影,证实血管完全正常的患者为对照组.比较各组患者外周血中CD62p,CD63和凝血酶敏感蛋白的阳性表达率.结果与结论:在相同抗血小板治疗6个月时,与金属裸支架组相比,药物洗脱支架置入对患者血小板活化的影响仍较明显,这可能与药物洗脱支架的晚期支架血栓形成增加有关.目前所提倡的12个月的标准抗凝治疗是否足够,以及血小板活化功能检测对支架置入治疗后抗血小板治疗的临床指导意义等仍需进一步研究.     

Evaluation of in-stent neointimal tissue components using integrated backscatter intravascular ultrasound: comparison of drug-eluting stents and bare-metal stents

Although in-stent restenosis (ISR) occurs after drug-eluting stents (DES) implantation, neointimal tissue characteristics have not been fully investigated. We assessed neointimal tissue components using integrated backscatter intravascular ultrasound (IB-IVUS) after DES and bare-metal stents (BMS) implantation. Fifty-seven consecutive patients with 61 lesions underwent repeated percutaneous coronary intervention (PCI) for the treatment of ISR (DES: 24 lesions, BMS: 37 lesions). PCI was performed using plain old balloon angioplasty (POBA). Before PCI, we assessed neointimal tissue characteristics using IB-IVUS. Neointima was divided into four categories: category 1 (-11 to -29?dB), category 2 (-29 to -35?dB), category 3 (-35 to -49?dB), and category 4 (-49 to -130?dB) according to IB values. We compared neointimal tissue components between DES and BMS. Thirty-three patients with 33 lesions (DES: 17, BMS: 16) were finally included. Neointima was predominantly composed of category 3 tissue in both groups (DES: 68?±?8%, BMS: 73?±?5%, P?=?0.053). DES had a broader distribution of category 4 tissue component than BMS. After POBA, distal slow flow phenomenon occurred in 5 of DES (29%), whereas none of BMS. In DES, the optimal threshold of category 4 tissue to predict distal slow flow phenomenon after POBA was 30% (sensitivity: 100%, specificity: 92%). Neointima was mainly composed of category 3 tissue at ISR site, irrespective of DES or BMS. In DES, there was a subgroup with category 4 rich tissue, which caused distal slow flow phenomenon after POBA. IB-IVUS might be useful to identify vulnerable neointima in DES restenosis.