抗CD34抗体优化雷帕霉素洗脱支架疗效的实验研究

目的 评价抗CD34抗体对雷帕霉素洗脱支架早期再内皮化以及远期抗再狭窄的影响.方法 将裸金属支架(BMS)、雷帕霉素洗脱支架(SES)和抗CD34抗体与雷帕霉素洗脱联合支架(ASES)随机置入到22头中华小型猪的冠状动脉内(共置入15枚BMS、17枚SES和16枚ASES).10头中华小型猪在置入支架(共置入6枚BMS、7枚SES和7枚ASES)后2周,另外12头中华小型猪在置入支架(共置入9枚BMS、10枚SES和9枚ASES)后3个月,进行冠状动脉造影及冠状动脉内光学相干断层成像( OCT)检查,并在处死动物后对支架段冠状动脉进行病理组织学检查及扫描电镜观察.结果 (1)支架术后2周,冠状动脉造影、OCT图像及支架段冠状动脉的病理组织学的观察均未发现支架内血栓及小的附壁血栓.对OCT图像的分析显示,ASES新生内膜覆盖率显著高于SES[ (55.56±35.27)％比(41.82±23.28)％,P＜0.05];ASES平均内膜覆盖厚度不但显著高于SES[(89.0±5.0)μm比(32.0±4.9) μm,P＜0.01],而且显著高于BMS[( 89.0±5.0) μ,m比(44.0±7.2)μm,P＜0.01].病理组织学观察及扫描电镜观察显示,ASES和BMS新生内膜覆盖水平及质量均优于SES.(2)支架术后3个月,定量冠状动脉造影显示ASES晚期支架内管腔丢失显著低于BMS [(0.18±0.06)mm比(0.35±0.06)mm,P＜0.05];对OCT图像的分析显示,ASES和SES新生内膜增生百分比均显著低于BMS[ (34.75±2.64)％和(35.63±2.07)％比(48.28±3.25)％,均P＜0.01];组织病理学分析显示,ASES和SES面积再狭窄百分比均显著低于BMS组[(28.65±5.64)％和(29.33±6.07)％比(46.18±8.25)％,均P＜0.05].结论 将抗CD34抗体联合应用到雷帕霉素洗脱支架上能够显著抵消后者在支架术后2周对再内皮化的抑制作用,同时没有削弱雷帕霉素洗脱支架术后3个月的抗再狭窄效能.     

雷帕霉素与CD34抗体联合支架系统的安全有效性研究

目的:观察药物与抗体联合支架是否安全,并与药物支架相比是否减少远期支架内再狭窄和晚期血栓形成。方法:选择60例冠状动脉造影提示靶病变为狭窄病变,随机分为两组,每组30例,分别置入雷帕霉素与CD34抗体联合支架系统(ASES),或雷帕霉素洗脱支架(SES),观察30天主要心脏不良事件和9个月晚期管腔丢失。结果:ASES治疗即刻效果与SES相似,9个月复查结果病变,经OCT检查证实,支架内血管直径比较,差异无统计学意义(P0.05)。靶血管重建率(%):ASES组10.83%,SES组5.40%,P0.05;ASES组内膜增生较SES组明显,内膜厚度平均(0.27±0.05)mm,SES组内膜厚度平均(0.12±0.07)mm。两组间比较,差异有统计学意义(P=0.033)。结论:ASES是安全的、有效的、血运重建率和支架内血栓形成比例均不高。并有血管内皮化更良好的特征。     

雷帕霉素洗脱支架治疗冠状动脉慢性完全性闭塞病变

目的:评价雷帕霉素洗脱支架在冠状动脉慢性(闭塞时间≥3个月)闭塞性病变治疗中的疗效。方法:86例冠状动脉造影显示慢性闭塞性病变患者,在成功重建冠状动脉血运后置入雷帕霉素洗脱支架(CypherTM, Cordis,Johnson & Johnson)50例(SES组),裸金属支架36例(BMS组),比较两组术后1年内各种不良心脏事件(死亡、心肌梗死、再次血管重建术和支架内血栓形成)的发生情况和再狭窄、再闭塞发生率。结果:SES组不良心脏事件发生率较BMS组显著降低(4．0％vs 19．4％,P<0．05)。SES组和BMS组分别有17例 (34．0％)和13例(36．1％)患者行冠状动脉造影复查,SES组较BMS组晚期丧失[(0．18±0．54)mm vs(0．85±0．98) mm,P<0．05]和再狭窄率(11．8％ vs 46．2％,P<0．05)显著降低。结论:雷帕霉素洗脱支架在冠状动脉慢性闭塞性病变治疗中可显著降低不良心脏事件的发生率和再狭窄发生率。     

光学相干断层成像评价植入不同药物洗脱支架后的血管愈合情况

目的应用光学相干断层成像（OCT）比较急性心肌梗死（AMI）患者植入不同药物洗脱支架（DES）后的新生内膜覆盖和支架贴壁情况以评估血管愈合。方法 49例AMI患者植入不同DES后9个月时进行OCT检查。其中20个雷帕霉素药物洗脱支架（SES,Cypher）,12个紫杉醇药物洗脱支架（PES,Taxus）和17个雷帕霉素衍生物药物洗脱支架（ZES,Endeavor）。每隔1mm评估OCT横断面影像每个支架柱的新生内膜覆盖和贴壁情况,同时观察每个支架内的血栓发生情况。结果总计对12378个支架柱进行了分析。SES的新生内膜增生最少,新生内膜厚度：SES（77±60）μm、PES（153±82）μm、ZES（265±130）μm,且新生内膜增生面积百分比最低,SES（10±8）%、PES（19±8）%、ZES（28±9）%,但SES和PES有更多未被新生内膜覆盖的支架柱,SES（15.1±16）%、PES（7.1±10）%、ZES（0.6±1.5）%,且贴壁不良支架柱的发生率也高于ZES,SES（3.8±7.2）%、PES（2.1±4.4）%、ZES（0±0）%,而有完全新生内膜覆盖的支架比例以ZES为高,SES5%、PES33.3%、ZES82.4%。血栓的发生率SES和PES高于ZES,SES34%、PES33%、ZES6%。结论 AMI患者植入不同类型DES后,其支架的新生内膜覆盖程度和贴壁不良的发生率是显著不同的,因此DES的类型可能影响了AMI血栓性病变的血管愈合过程。     

雷帕霉素洗脱支架治疗冠脉左前降支近中段病变的临床疗效评价

目的评价雷帕霉素洗脱支架治疗冠脉左前降支近中段病变的临床疗效。方法以冠脉造影显示左前降支近中段狭窄病变并分别置入雷帕霉素洗脱支架(SES组)或裸金属支架(BMS组)的患者各100例为研究对象。记录患者的一般情况、临床和冠脉病变特征,术后1年临床随访和冠脉造影复查。结果两组患者匹配良好,仅SES组置入支架的长度显著长于BMS组(21.07±7.45mmvs18.25±6.82mm,P=0.0057)。在随访中,无心源性死亡,SES组1例因支架内再狭窄发生急性心肌梗死。冠脉造影复查显示SES组再狭窄率较BMS组显著降低(7.4%vs25.9%,P=0.002),并直接导致不良事件发生率的下降。结论药物洗脱支架显著降低左前降支近中段狭窄病变介入治疗后再狭窄发生率,可作为血运重建的一种有效策略。     

光学相干断层成像比较猪冠状动脉西罗莫司洗脱支架与佐他莫司洗脱支架置入后早期新生内膜覆盖情况

目的应用光学相干断层成像(OCT)比较西罗莫司洗脱支架(SES)与佐他莫司洗脱支架(ZES)置入后1月内新生内膜覆盖情况。方法 18只中华小型猪平均分为3组,每只猪分别在前降支和右冠状动脉随机置入SES和ZES支架各一枚,3组实验动物分别在第7天、14天、28天进行OCT检查,测量新生内膜厚度、支架内面积、管腔内面积、新生内膜面积、面积狭窄百分比和新生内膜覆盖率,比较ZES与SES置入后1月内新生内膜覆盖情况。结果 OCT测量结果显示,支架置入7天和14天时,ZES与SES两种支架丝表面新生内膜厚度和新生内膜覆盖率均存在显著统计学差异(P<0.001)。同样支架术后28天时ZES与SES支架丝表面新生内膜厚度存在显著统计学差异(244.3±282.3μmvs136.3±91.1μm,P<0.001),新生内膜覆盖率存在显著差异(94.88%±2.93%vs90.96%±4.35%,P=0.008)。结论在支架置入后1个月内,ZES与SES比较新生内膜增生更显著,支架丝表面新生内膜覆盖率更高。     

莪术组分涂层支架预防猪冠状动脉再狭窄的研究

目的通过中华实验用小型猪冠状动脉再狭窄模型,观察中药莪术组分涂层支架抑制内膜增殖的有效性。方法将18只小型猪随机分为莪术组分涂层支架组(ZES组)、雷帕霉素涂层支架组(SES组)及金属裸支架组(BMS组),每组6只,分别在左前降支、左回旋支及右冠状动脉置入同一种支架各1枚。术后30 d冠状动脉造影后将猪处死,观察支架血管段的病理形态及影像学变化。结果 30 d时,与BMS组比较,ZES组和SES组平均管腔直径和平均管腔面积均明显增大(P<0.05),直径狭窄率和面积狭窄率明显减小(P<0.05);与SES组比较,ZES组和BMS组炎症积分明显降低,内皮化积分明显升高(P<0.05);3组损伤积分比较,差异无统计学意义(P>0.05);光学相干断层扫描及扫描电镜观察,SES支架组30 d时可见部分支架节段内皮化不全及炎性细胞浸润。结论 ZES支架可有效地抑制血管内膜增殖,具有良好的生物相容性。     

光学相干断层显像评价药物洗脱支架置入后内膜增殖和血栓形成

目的 应用光学干涉断层显像(OCT)技术评价雷帕霉素洗脱支架(SES)置入后3个月和2年后内膜增殖和支架内血栓形成情况.方法 对3个月组进行SES置入后3个月的OCT随访观察,对2年组进行SES置入后2年的随访观察.测量每一个支架支撑杆表面的新生内膜厚度,并评估无内膜覆盖支架支撑杆及支架内血栓形成情况.结果 2年组的内膜厚度显著大于3个月组[(71±93)μm比(29±41)μm,P＜0.01],而2年组中的无内膜覆盖支架支撑杆的比例明显低于3个月组(5%比15%,P＜0.01).2年组与3个月组无内膜覆盖支撑杆患者的比例差异无统计学意义(81%比95%,P＞0.05).两组中均有14%的患者出现无临床症状的支架内血栓形成.结论 SES置入后3个月到2年新生内膜的增生在不断进展,无内膜覆盖支撑杆数明显减少.但是直到支架置入后2年,多数患者体内仍然存在部分无内膜覆盖的支架支撑杆.     

冠状动脉支架置入后血栓形成的原因和机制

自1987年支架置入术应用于经皮冠状动脉介入治疗（percutanenous coronary intervention,PCI）领域以来,成功解决了单纯PTCA术的急性血管弹性回缩导致再狭窄的问题,但金属裸支架（bare-metal stents,BMS）仍然有约30%的再狭窄率,而药物洗脱支架,特别是雷帕霉素和紫杉醇药物支架的出现,将再狭窄率进一步降至10%以内,随后关于DES与支架内血栓的临床研究显示：雷帕霉素和紫杉醇作为细胞有丝分裂抑制剂,在抑制平滑肌细胞的同时,也抑制了内皮细胞增殖,从而可能导致支架内血栓甚至支架内再狭窄（in stent restenosis,ISR）,本文将对DES再狭窄与支架血栓可能存在的原因和机制作一综述。     

内皮祖细胞CD34抗体包被冠脉支架对猪冠状动脉再狭窄影响的研究

目的 探讨生物可降解高分子载内皮祖细胞CD34抗体支架是否可降低猪冠状动脉支架置入术后再狭窄.方法 以生物可降解高分子聚乙二醇-聚乳酸-聚谷氨酸共聚物为载体,应用N-琥珀酰亚胺基-3-(2-吡啶二硫)-丙酸酯(SPDP)方法制成内皮祖细胞CD34抗体洗脱支架.18只猪随机分为三组,即紫杉醇支架组、CD34抗体支架组、裸支架组,每组6只,将紫杉醇支架、CD34抗体支架、裸支架分别植入到各组猪的冠状动脉损伤段,4 w后处死,取出支架段血管行病理学观察及计算机图像分析血管管腔面积、内膜增生面积以及面积狭窄百分比.结果 CD34抗体支架组内膜增生面积较裸支架组减低(P＜0.05),紫杉醇支架组内膜增生面积较裸支架组也减低(P＜0.05),但较CD34抗体支架组无明显差别(P＞0.05).结论 生物可降解高分子载内皮祖细胞CD34抗体支架可明显加速支架置入术后血管内皮修复,降低再狭窄的发生.     

The union of anti-CD34 antibody can improve the performance of drug-eluting stents

Objectives : The authors investigate whether the combination of anti‐CD34 antibody with DES is win–win cooperation. Background : DES may reduce the risk of restenosis compared to bare‐metal stents (BMS), but they were found to inhibit the healing process of intima. Methods : Fifteen BMS, 17 DES, and 16 combined anti‐CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments. Results : After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in‐stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES. Conclusion : The combination of anti‐CD34 antibody and DES can not only well offset the short‐term inhibitory effect on re‐endothelialization but also slightly enhance the long‐term antiproliferative effect. © 2011 Wiley Periodicals, Inc.     

雌二醇洗脱支架抑制血管内膜增生的实验研究

目的观察雌二醇(E2)洗脱支架植入对高脂喂饲兔腹主动脉内膜增生的影响,并探讨其可能的机制。方法雄兔高脂喂饲后分别于腹主动脉植入裸金属支架、磷酸胆碱(PC)涂层支架和17β-E2洗脱支架,应用HE染色、免疫组化染色及蛋白印迹方法观察17β-E2洗脱支架抑制内膜增生的作用及机制。结果支架植入术后血管壁ERK迅速活化,磷酸化ERK(p-ERK)在术后0.5 h时达峰值。各组支架植入12周时血管内膜均明显增厚。E2洗脱支架组新生内膜面积较裸金属支架组减少36%。支架植入后0.5 h时E2洗脱支架组p-ERK表达明显低于裸金属支架组。2周时E2洗脱支架组内皮化率明显高于裸金属支架组及PC涂层支架组。结论 E2洗脱支架安全、有效,可明显减少实验兔支架植入后的血管内膜增生;与普通裸金属支架对比,E2洗脱支架能够加速支架段血管的再内皮化;丝裂原激活蛋白激酶ERK1/2可能介导了支架植入后血管平滑肌细胞的增殖和内膜增生。     

Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization

Restenosis is a direct result of vessel injury, local inflammation, and remodeling following balloon angioplasty and coronary stenting resulting in luminal narrowing. The process involves a complex interplay of released growth factors that stimulate smooth muscle cells (SMCs) to migrate and proliferate, as well as activating endothelial cells (ECs) at injury sites. The latter re-establishes the luminal endothelial monolayer that keeps a barrier to circulating cells from underlying extracellular matrix and SMCs. Understanding the cellular mechanisms of intimal hyperplasia and re-endothelialization is important in that uncontrolled cellular processes account for coronary luminal narrowing, leading to the recurrence of clinical symptoms, hospitalizations, and repeat interventions. The evolution of drug-eluting stents that inhibit intimal hyperplasia has revolutionized percutaneous coronary interventions in that potential late luminal narrowing is attenuated. Sirolimus and paclitaxel are two medications utilized for their efficacy at inhibiting intimal hyperplasia and subsequent clinical events. The effects of these drugs on EC biology have not been well investigated. This article discusses basic cellular processes of vessel repair after balloon angioplasty and stenting, and focuses on the differential molecular mechanisms of sirolimus and paclitaxel towards proliferation and migration. These drugs inhibit both SMC and EC proliferation, but by different mechanisms, and paclitaxel inhibits EC migration, whereas sirolimus does not. Their discriminating effects towards re-endothelialization may clinically differentiate these two drugs. Inhibiting re-endothelialization may translate into more adverse clinical events.     

Morphological and histological studies of in-stent restenosis in seven types of stents implanted in porcine coronary arteries]

OBJECTIVES: Differences in the mechanism of restenosis after stenting between coil and tubular stents were examined in porcine coronary arteries using histological and immunohistochemical methods. METHODS: Twenty-four pigs underwent balloon-induced injury in the left anterior descending coronary artery. Two weeks later, seven different stents clinically available in Japan (Coil stents: GR I, GR II, Wiktor, Cordis; Tubular stents: gfx, Multilink, Palmaz-Schatz) were implanted in the injured site. Four weeks after the stent implantation, the pigs were sacrificed for histological examination and for morphometrical analysis of the lumen, neointima, media and adventitia. Immunohistochemical studies using anti-proliferating cell nuclear antigen (PCNA), anti-alpha-smooth muscle actin and anti-macrophage antibody were also performed. RESULTS: The coil stents formed eccentric, and the tubular stents formed concentric neointimal proliferation. Although there was no difference in the area of neointima between the stents, the area of lumen in the tubular stents was bigger than that in the coil stents (p < 0.01), because the vascular area was bigger in the tubular stents (p < 0.05). Immunohistochemical examination found many PCNA-positive cells in the proliferated neointima, especially in the area around the stent strut. Many of these cells around the stent strut were positively stained by anti-macrophage antibody. Other cells positively stained for PCNA were confirmed as smooth muscle cells. CONCLUSIONS: Tubular stents maintained a wider lumen than coil stents, because negative remodeling after stenting was less in the tubular stents. Implantation of stents with less negative remodeling is very important to prevent restenosis after stenting.     

Vascular Endothelial Growth Factor–Bound Stents: Application of In Situ Capture Technology of Circulating Endothelial Progenitor Cells in Porcine Coronary Model

Objectives

We evaluated the in vivo performance of a newly devised vascular endothelial growth factor (VEGF)‐bound stent in a porcine coronary model.

Background

An anti‐CD34 antibody‐bound stent, which captures endothelial progenitor cells (EPCs) to accelerate tissue formation, did not reduce intimal hyperplasia. By targeting the VEGF receptor, which is expressed on endothelial‐lineage cells, we developed VEGF‐bound stents that may enable selective capture of EPCs followed by rapid endothelialization.

Methods

Metallic stents were first coated with poly‐(ethylene‐co‐vinyl alcohol), and then chemically bound with either VEGF or anti‐CD34 antibody. These stents were placed in porcine coronary arteries for up to 14 days. Stent surface was evaluated by immunohistochemistry and by scanning electron microscope (SEM).

Results

After 2‐day stenting with VEGF‐bound stents, small populations of KDR (VEGF receptor‐2)‐positive cells adhered to the stent struts. After 7‐ and 14‐day stenting, struts were fully covered with newly regenerated tissue. SEM images showed that the uniform tissue formed on struts was morphologically similar to native endothelium and was continuously connected with adjacent native endothelium. On the other hand, for the anti‐CD34 antibody‐bound stents, stent struts were rapidly covered by newly generated tissue that consisted of multicellular aggregates.

Conclusions

Compared with anti‐CD34 antibody‐bound stents, VEGF‐bound stents provide highly selective capture of EPCs, followed by rapid formation of intact endothelium tissue at an early period of stenting. These results suggest that VEGF‐bound stents could represent a promising therapeutic option for cardiovascular stenting, although further long‐term follow‐up experiment with double‐blinded fashion is needed prior to clinical application. (J Interven Cardiol 2014;27:63–72)

     

Vascular endothelial growth factor (VEGF)-eluting stents: in vivo effects on thrombosis, endothelialization and intimal hyperplasia

Local drug delivery by stent can reduce in-stent restenosis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen. After stenting, the arterial wall is almost denuded of endothelium. This loss of endothelium contributes to the smooth muscle cell (SMC) proliferation seen in restenosis, since the endothelium actively inhibits SMC hyperplasia. Over time, the endothelium recovers and SMC hyperplasia is arrested. The capacity of VEGF-coated stents to accelerate re-endothelialization, and to therefore reduce restenosis and thrombosis, was tested in this study. Radiolabeled VEGF was absorbed onto stents and released over nine days in an in vitro perfusion circuit. VEGF-coated stents were deployed in arterial segments to study local tissue release. A New Zealand White rabbit iliac artery model for stent implantation was used. Re-endothelialization and thrombosis were assessed after seven days. Further animals were examined 28 days post-procedure for in-stent restenosis. Stented vessels were resin-embedded, sectioned and stained. Intimal thickening was calculated using computerized morphometry. In vitro, the stents released 80% of the initial load over nine days. At seven days, thrombus was significantly reduced (12.5 mg for controls versus 0 mg for VEGF; p = 0.014). No beneficial effect was seen on endothelialization, nor on intimal hyperplasia. Neointimal area was 2.2 0.9 mm2 for controls versus 2.4 1.8 mm2 for VEGF (p = 0.8). These VEGF-eluting stents do not accelerate re-endothelialization or inhibit restenosis. Stent thrombosis appears to be reduced, which may make these stents less thrombogenic and be valuable in higher-risk cases.     

OCT评估可降解聚合物DES术后血管修复研究进展

与裸金属支架相比,第1代药物洗脱支架（drug-eluting stent,DES）显著提高了治疗的有效性,但其永久聚合物涂层使得支架植入后内皮化延迟、血管修复受损,导致晚期支架内血栓的发生率明显升高。在此基础上新一代DES应运而生,可降解聚合物DES作为其典型代表,通过优化设计等明显改善了其植入后血管修复的进程。光学相干断层成像（OCT）作为目前分辨率最高的血管腔内影像学技术,可用于评估支架植入后内皮覆盖程度,判断血管修复情况,预测血栓性事件发生风险。本文将主要对OCT评估可降解聚合物DES植入术后血管修复及再内皮化做一综述。     

Does platelet glycoprotein IIb/IIIa receptor antibody improve in-hospital outcome of coronary stenting in high-risk thrombus containing lesions?

Coronary stenting in acute coronary syndromes probably increases the risk of acute stent thrombosis. Recently, use of platelet glycoprotein IIb/IIIa receptor antibody has been shown to improve percutaneous transluminal coronary angioplasty (PTCA) outcomes in high risk lesions. The purpose of this analysis was to determine safety and efficacy of platelet glycoprotein IIb/IIIa receptor antibody administration in patients receiving coronary stents in high-risk lesions. Between October 1995 and November 1996, 282 patients with acute ischemic syndromes received coronary stents at our center: 73 had thrombus containing lesions—40 presented with AMI and 33 with unstable angina and make up the study population. The mean age of these patients was 61 ± 13 years, 56 were male, 35 had a history of myocardial infarctions (MI), 21 had prior coronary artery bypass graft (CABG), and 21 had prior PTCA. Coronary stenting was used for suboptimal result in 46 patients (63%), threatened closure in 25 patients (34%), and acute closure in 2 patients (3%). Platelet glycoprotein IIb/IIIa receptor antibody was administered during the procedure in 74% and after the procedure in 26%. A total of 115 stents were deployed (Gianturco-Roubin 80, Palmaz-Schatz 29, and Wallstent 6) in 24 LAD, 21 RCA, 15 LCX, and 13 saphenous vein graft (SVG) lesions. Procedural success was 100%. The mean diameter stenosis before and after intervention was 60% ± 31% and 4% ± 14%, respectively. In-hospital events included 1 Q-wave MI (1.4%), 13 non–Q-wave MI (18%), and 1 death (1.4%). There was no subacute stent thrombosis, emergency CABG, or repeat PTCA. Significant in-hospital bleeding complications were noted in seven (10%) patients, with five patients (6.8%) requiring blood transfusions. In this series of patients with acute ischemic syndromes associated with angiographic evidence of thrombus, combined use of platelet glycoprotein IIb/IIIa receptor antibody and stenting resulted in a very low incidence of subacute stent thrombosis and emergency target lesion revascularization. However, bleeding complications were higher than expected with conventional antiplatelet therapy following routine stenting. Cathet. Cardiovasc. Intervent. 46:415–420, 1999. © 1999 Wiley-Liss, Inc.     

The conundrum of late and very late stent thrombosis following drug-eluting stent implantation

PURPOSE OF REVIEW: Drug-eluting stents reduce restenosis compared with bare metal stents, but there is growing concern that drug-eluting stents may lead to higher rates of late stent thrombosis, a rare and potentially catastrophic complication following stenting. RECENT FINDINGS: While the data on the risk of late stent thrombosis are not definitive, several general conclusions may be drawn from the available data. Late thrombosis, while associated with high mortality and morbidity, is an uncommon complication of both drug-eluting stents and bare metal stents. Randomized trials of approved drug-eluting stents versus bare metal stents have shown additional cases of late stent thrombosis in drug-eluting stents, but no significant difference in the cumulative incidence of stent thrombosis, myocardial infarction, or cardiac death at 4 years of follow-up. Observational studies suggest higher very late stent thrombosis incidence, but the relative risks of drug-eluting stents versus bare metal stents in specific high-risk groups require further study. Although the etiology of late stent thrombosis is multifactorial, premature discontinuation of clopidogrel appears to be the most important risk factor. SUMMARY: Long-term follow-up of patients after coronary stenting has identified stent thrombosis as a rare but serious event. Ongoing clinical trials in broader patient populations will be helpful to understand the risk of late stent thrombosis with greater certainty.