Drug‐eluting stent fracture: Incidence,contributing factors,and clinical implications

Stent fracture has been observed in noncoronary vessels, especially in the superficial femoral and popliteal arteries and with bare metal stents in saphenous vein grafts of coronary arteries. Since the introduction of drug‐eluting stents, stent fractures have also been reported in small studies and case reports. We reviewed these publications to assess what is known regarding the incidence, contributing factors, and clinical implications of drug‐eluting stent fracture in coronary arteries. The reported rate of drug‐eluting stent fracture in coronary arteries ranges from 1 to 8%, although much of the available literature is derived from single‐center studies that are heterogeneous in their study methods. A higher risk of stent fracture may be associated with the right coronary artery location, excessive tortuosity or angulation of the vessel, overlapping stents, and longer stents. The closed‐cell design of the Cypher stent has been associated with increased rigidity that may increase the risk of stent fracture, although these studies did not assess the overall outcomes between the Cypher and Taxus stents in a head‐to‐head comparison. Stent fracture has been shown by most studies to be associated with a statistically increased incidence of focal in‐stent restenosis, and some have shown an increased risk of target lesion revascularization. Other complications observed with stent fracture include stent thrombosis, coronary aneurysms, myocardial infarction, and sudden death. © 2009 Wiley‐Liss, Inc.     

药物洗脱支架断裂的影像认识

目的借助冠状动脉造影和血管内超声的影像资料,确定支架断裂的发生和类型。方法回顾性分析北京大学人民医院2 021例冠状动脉造影和183例血管内超声（IVUS）影像资料。结果共发现3例患者的6处支架断裂,其中2例经IVUS证实。3例支架断裂均发生在西罗莫司药物洗脱支架,且均发生在冠状动脉介入术后1年以内。冠状动脉造影证实4处支架断裂为完全断裂伴断裂处支架移位。IVUS证实3处支架断裂为完全断裂,2处为部分断裂;1处断裂靠近支架重叠处;1处支架断裂伴有血管瘤形成。结论冠状动脉造影和IVUS可以帮助确定支架断裂的诊断。     

西罗莫司洗脱支架术后极晚期血栓形成四例分析

目的回顾性分析西罗莫司洗脱支架术后发生极晚期支架内血栓形成患者的临床资料。方法2002年10月至2005年8月,共612例患者置入835枚西罗莫司洗脱支架,其中4例患者（0．65％）于2006年1至8月发生极晚期支架内血栓形成,导致急性前壁ST段抬高的心肌梗死再次入院。回顾性分析该4例患者的临床情况、抗血小板药物应用情况、造影结果以及PCI过程等相关资料。结果4例患者均为男性,年龄40～69岁,血栓发生时间为术后31～37个月。患者第一次支架术后服用氯吡格雷7～12个月,其中1例患者血栓发生前18个月停用阿司匹林。支架置入部位均为前降支,急诊造影提示支架内闭塞,局部可见明显血栓征象,前向血流TIMI0级,均再次行PCI治疗后存活。结论药物洗脱支架术后可以发生极晚期血栓形成,药物洗脱支架术后的远期随访问题值得重视。     

Very late stent thrombosis due to DES fracture: Description of a case and review of potential causes

Stent fracture and subsequent stent thrombosis are known complications after stent implantation, especially in stents with closed cell design like the first generation sirolimus drug eluting stents (DES). Late stent thrombosis is very rarely encountered in our patient population, majority Chinese. We report a case of non‐ST elevation myocardial infarction as a result of very late stent thrombosis (three years after implantation) due to stent fracture at the site of overlap of two first generation sirolimus DES. There were initial difficulties in restoring coronary flow by conventional reperfusion therapies but a successful outcome after implantation of an endothelial progenitor cell capture stent, with no further recurrence of ischemic event after 12 months. An attempt was made to analyze all existing factors present and contributing to the stent fracture and stent thrombosis in this case, as reported in the literature. © 2011 Wiley Periodicals, Inc.     

Very late thrombosis after implantation of sirolimus eluting stent

Stent thrombosis after sirolimus eluting stent implantation has been reported to occur at six hours to 375 days after the procedure and usually within the two weeks after discontinuation of antiplatelet medication. A case is reported of very late stent thrombosis after 17 months of sirolimus eluting stent implantation and eight months after clopidogrel discontinuation despite aspirin continuation. This case underlines the possible need for long term antiplatelet medication among patients receiving sirolimus eluting stents.     

Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome

The use of drug eluting stents constitutes a major breakthrough in current interventional cardiology because it is more than halves the need of repeat interventions. It is incontrovertible that coronary stents, in general, have been beneficial for the vast majority of patients. A small increase in thrombosis, following DES implantation, is offset by a diminished risk of complications associated with repeat vascularization. However, late and, especially, very late stent thrombosis is a much feared complication because it is associated with myocardial infarction with increased mortality. Despite that stent thrombosis is thought to be multifactorial, so far clinical reports and reported pathology findings in patients died from coronary stent thrombosis as well as animal studies and experiments, point toward a hypersensitivity inflammation. The stented and thrombotic areas are infiltrated by interacting, via bidirectional stimuli inflammatory cells including eosinophils, macrophages, T-cells and mast cells. Stented regions constitute an ideal surrounding for endothelial damage and dysfunction, together with hemorheologic changes and turbulence as well as platelet dysfunction, coagulation and fibrinolytic disturbances. Drug eluting stent components include the metal strut which contains nickel, chromium, manganese, titanium, molybdenum, the polymer coating and the impregnated drugs which for the first generation stents are: the antimicrotubule antineoplastic agent paclitaxel and the anti-inflammatory, immunosuppressive and antiproliferative agent sirolimus. The newer stents which are called cobalt-chromiun stents and elute the sirolimus analogs everolimus and zotarolimus both contain nickel and other metals. All these components constitute an antigenic complex inside the coronary arteries which apply chronic, continuous, repetitive and persistent inflammatory action capable to induced Kounis syndrome and stent thrombosis. Allergic inflammation goes through three phases, the early phase, the late phase and the chronic phase and these three phases correspond temporally with early (acute and sub acute), late and very late stent thrombosis. Bioabsorbable allergy free poly lactic acid self expanding stents, nickel free stainless steel materials, stent coverage with nitric oxide donors and antibodies with endothelial progenitor cell capturing abilities as well as stents eluting anti-inflammatory and anti-allergic agents might be the solution of this so feared and devastating stent complication.     

State of treatment of coronary artery disease by drug releasing stents

BACKGROUND: Despite improved technologies restenosis remains the main drawback of catheter-based interventions in coronary artery disease. Local application of anti-proliferative drugs through drug releasing stents is a promising concept addressed to solve this problem. DRUG RELEASING STENTS: Today, given the technical capabilities for controlled drug release from coronary stents, the development of drug eluting stents has emerged as one of the main research areas in interventional cardiovascular medicine. Several different approaches for drug loading on coronary stents as well as a variety of antiproliferative and anti-inflammatory agents, such as paclitaxel, actinomycin D, sirolimus, tacrolimus, everolimus and dexamethasone are under clinical investigation. RESULTS: Since the first enthusiastic reports from first in-man observations with drug coated stents, the success of the combination of both a biological and a mechanical approach has been proved in several controlled studies with restenosis rates between 0% in the RAVEL trial (sirolimus, Cordis Bx Velocity trade mark stent), 0% in the TAXUS I trial (paclitaxel, Boston Scientific NIRx trade mark stent) and 4% in the ASPECT Study (paclitaxel, Cook V-Flex plus trade mark stent). The risk of stent thrombosis seems to depend on the dose of the antiproliferative drug - in the SCORE trial stent thrombosis occurred in 6.3% of patients with high dose of QP2 and the antiplatelet therapy, in the ASPECT subgroup with cilostazol instead of clopidogrel and high dose of paclitaxel in up to 25%, whereas in RAVEL and TAXUS I no stent thrombosis was observed. CONCLUSION: If the "one digit" restenosis rate observed in clinical trials could be confirmed in clinical practice without increase of complications, especially stent thrombosis using multiple and/or long stents, we can expect in the near future that implanting drug eluting stents in larger patient groups and lesion subsets will cause a reduction of patients with need for surgical revascularization.     

A completely fractured zotarolimus‐eluting stent in an aortocoronary saphenous vein bypass graft

Drug‐eluting stents (DES) have significantly improved the rate of target vessel revascularization in comparison with bare metal stents. DES fracture was not reported in multicenter randomized clinical trials, but several case reports of DES fracture have been published, mostly with sirolimus‐eluting stents. DES fracture is associated with stent restenosis and thrombosis. We report a zotarolimus‐eluting stent fracture in an aortocoronary saphenous vein graft (SVG) bypass. The patient presented with chest pain and a non‐ST‐elevation myocardial infarction. He underwent cardiac catheterization that showed a complete fracture of a zotarolimus‐eluting stent in the ostium of a sequential SVG to the diagonal and obtuse coronary arteries. His management included coronary angioplasty and retrieval of the proximal fractured segment. We discuss the potential causes for this stent fracture and suggest caution when using a DES in an ostial location of a SVG bypass, especially in a highly mobile vessel. © 2012 Wiley Periodicals, Inc.     

Strategies for drug‐eluting stent treatment of bifurcation coronary artery disease in the United States: Insights from the e‐Cypher S.T.L.L.R.Trial

Objectives: Our goal is to report the first large multicenter data for percutaneous coronary intervention (PCI) of bifurcation disease with drug‐eluting stents (DES) in the United States. Background: Bifurcation PCI remains a challenge to this date. There are limited data on outcomes of patients treated with bifurcation DES implantation, particularly in the United States. Methods: There were 161 patients with bifurcation disease [side branch (SB) ≥2‐mm] treated with ≥1 sirolimus‐eluting stents at 41 centers participating in the Stent deployment Techniques on cLinicaL outcomes of patients treated with the cypheR?stent (STLLR) trial. There was no protocol mandated strategy for bifurcation PCI. One‐year outcome data were collected. Angiographic and clinical data were adjudicated independently. Results: There were 147 patients (91.3%) treated with single stent strategy. Only 14 (8.7%) patients received sirolimus‐eluting stents implantation in both branches. Among patients with single stent strategy, double wire strategy (DW) was selected in 27 (18.4%) patients whereas single wire strategy (SW) was selected in 120 (81.6%) patients. There were 48 (32.7%) Medina 1,1,1 bifurcations treated with SW (n = 34; 70.8%) and DW (n = 14; 29.2%). There were 26 procedures started with SW which had SB dilatation during the procedure, one as a bailout (TIMI‐1 grade flow in the SB). Overall 1‐year death, myocardial infarction, and target lesion revascularization occurred in 2.4, 4.0, and 5.6%, respectively. There was no significant difference in clinical outcomes between SW and DW. SB dilatation was associated with a high rate of stent thrombosis (8.6%). Conclusions: Main branch stenting without SB protection is the most common approach utilized in the STLLR study, which may reflect contemporary DES bifurcation strategies in the Unite States. This strategy was associated with an acceptable low incidence of adverse outcomes at 1‐year. © 2009 Wiley‐Liss, Inc.     

Infrapopliteal drug‐eluting stents for chronic limb ischemia

Objective: We report our experience with the elective placement of below‐knee, drug‐eluting stents in patients with chronic limb ischemia. Background: Infrapopliteal percutaneous transluminal angioplasty has been associated with a lower rate of procedural success and high rate of restenosis because of the small size of the tibial vessels and the prevalence of calcified and diffuse atherosclerotic disease. Prior published data reports 3‐year patency rates below 25%. Bare metal stents have been reported in bailout situations. Drug‐eluting stents have markedly reduced restenosis compared to bare metal stents in the coronary vasculature, but there is little data supporting the use of these devices below the knee. Methods: Elective placement of drug‐eluting stents in infrapopliteal lesions was performed on 10 patients with severe (≥Fontaine Stage IIb) claudication (n = 1) or limb‐threatening ischemia (n = 9) (rest pain, nonhealing ulcers and gangrene). Results: A total of 17 drug‐eluting stents were electively placed in 12 below‐knee arteries in 10 patients, resulting in an average of 1.7 ± 0.7 stents per patient. The mean lesion length was 24.8 ± 10.9 mm, the mean total stent length was 38.3 ± 19.1 mm, and the mean nominal stent diameter was 2.8 ± 0.3 mm. One patient required target vessel revascularization (TVR) at 3 weeks because of stent thrombosis. TVR was 10% at 12.4 ± 6.5 months of follow‐up. Clinically driven angiography in three different patients was performed at 4, 15, and 16 months and confirmed drug‐eluting stent patency in each case. Conclusions: The use of below‐knee drug‐eluting stents is feasible and appears to be safe in our small series of complex infrapopliteal lesions causing chronic limb ischemia. The occurrence of a single case of stent thrombosis warrants continued observation in this cohort. Prospective clinical trials will be necessary to confirm the benefits and justify the costs of this strategy for treating patients with infrapopliteal culprit lesions and chronic limb ischemia. © 2008 Wiley‐Liss, Inc.     

Decreased risk of stent fracture‐related restenosis between paclitaxel‐eluting stents and sirolimus eluting stents: Results of long‐term follow‐up

Objective: To compare the outcomes between paclitaxel‐eluting stents (PES) and sirolimus‐eluting stents (SES) for the treatment of drug‐eluting stent (DES) fracture. Background: DES fracture is considered as an important predictor of in‐stent restenosis (ISR). However, little data are available evaluating the optimal treatment for this complication of coronary stenting. Methods: From January 1, 2004 to December 31, 2008, patients with DES ISR treated with a second DES were identified and evaluated for stent fracture. Stent fracture was defined by the presence of strut separation in multiple angiographic projections, assessed by two independent reviewers. Target lesion revascularization (TLR) at 6 and 12 months were the primary end points. Results: Of 131 lesions with DES ISR treated with a second DES, we found 24 patients (24 lesions, 18.2%) with angiographically confirmed stent fracture. Of these, 20 patients (20 lesions) treated with either PES (n = 11/55%) or SES (n = 9/45%) were included in the study. TLR at 6 months occurred in 9% of patients treated with PES and 22% of those treated with SES (P = 0.41). After 12 months, TLR was 9% and 55.5%, respectively (P = 0.024). Conclusions: This study demonstrates a high incidence of stent fracture in patients presenting with DES ISR in need of further treatment with another DES. The suggested association between treatment of stent fracture‐associated DES ISR with PES as compared with SES, and better long‐term outcomes, is in need of confirmation by larger prospective registries and randomized trials. © 2011 Wiley Periodicals, Inc.     

急性冠脉综合征患者药物洗脱支架雷帕霉素CypherTM植入后的不良反应分析

目的:分析雷帕霉素药物洗脱支架CypherTM植入后对急性冠脉综合征患者近、远期的不良反应.方法: 选择接受CypherTM治疗的冠心病患者83例,在支架植入术后9个月内全部接受门诊随访及冠脉造影,了解支架内急性和亚急性血栓、边缘效应、贴壁不良现象、支架处动脉瘤发生率及相应的不良心脏事件(MACE)发生情况.结果:83例患者共植入支架112个,植入成功率为98.8%(82/83).29例(34.9%)接受冠脉造影,MACE9例,发生率10.8%(9/83),其中,1例术中发生猝死,1例术后3d因亚急性血栓造成再发心肌梗死,其余7例在出院后1～3 月内发生心绞痛,皆经造影证实为血栓形成,再次成功靶血管血运重建8例;其余20例无症状患者造影发现支架边缘狭窄(无血栓)2例,总再狭窄为13.3%(11/83);无动脉瘤发生.9例MACE中,有弥漫病变5例,其中4例植入长支架,1例植入重叠支架,其余为简单病变;29例患者共发现贴壁不良现象5例,皆发生MACE,其中4例为弥漫病变植入长支架,1例为简单病变.结论:急性或亚急性血栓形成是药物支架CypheTM植入后出现的主要不良反应,可能与弥漫病变植入长、重叠支架引起贴壁不良有关.     

Multiple stent fractures at the site of coronary artery bypass insertion

Drug eluting stents have led to a substantial reduction of in‐stent restenosis. Stent fracture (SF) is an important cause for the cases of restenosis which still occur. Sites of increased vessel movement, long stents, and overlapping stents have been observed to be more prone to fracture. We report the case of a patient with multiple drug eluting SFs at the site of coronary artery bypass insertion. The decision to implant stents at the site of bypass insertion should be made carefully. SF should be considered when gaps between previously implanted stents are observed. © 2008 Wiley‐Liss, Inc.     

Sirolimus‐eluting stent fracture detection by three‐dimensional optical coherence tomography

Stent fracture has emerged as a complication of drug‐eluting stent and is now recognized as contributing to in‐stent restenosis and possibly stent thrombosis. Although optical coherence tomography (OCT) can detect stent fractures in the absence of circumference struts, it is challenging to visualize stent fractures with only cross‐sectional OCT images. We describe two cases of restenosis with stent fracture detected by a novel three‐dimensional OCT image reconstruction technique. This technique allows identification of a single stent fracture even in the absence of angiographic signs. © 2011 Wiley Periodicals, Inc.     

Drug eluting stents: from evidence based medicine to clinical practice

Drug eluting stents have been developed in order to reduce in-stent restenosis observed with a 20 to 40% rate in bare-stents. Neoinitimal smooth muscular cells proliferation have been characterized as the corner stone of in-stent restenosis. Consequently, many anti-mitotic and anti-inflammatory drugs have been evaluated in a new stent generation, so called coated stents or drug eluting stents. Three major components must be considered to evaluate the beneficial effects: the bare-stent, the drug, and the deliverance system, most usually a polymer. For the present, sirolimus eluting stent and paclitaxel eluting stent are available in the market with the european conformity label considering evidence based medicine established in randomized trials. Both stents have been shown to reduce in-stent restenosis incidence to less than 7%. Long-term follow-up still remain expected and would give answers to two safety queries: what is about the incidence of late stent thrombosis, what is about mal-apposition consequences in clinical feature. Utilization of drug eluting stent in clinical practice must considered materials with european conformity and must applied French society of cardiology guidelines restricting implantation to patients who meet high-risk restenosis criteria. Medicoeconomic approach must be considered beneficial at the present only in patients with high restenosis risk. Long-term antiplatelet regimen of aspirin and clopidogrel must be considered to avoid late stent thrombosis.     

Diffuse coronary ectasia and intracoronary thrombus involving left circumflex coronary artery and presenting as acute coronary syndrome: report of two cases

Stent thrombosis is a feared complication of percutaneous coronary intervention. Promises and problems, late complications and early stent thrombosis have been reported after drug eluting stents implantation too. Moreover some patients with imperative cardiologic indications for combination therapy with aspirin and clopidogrel (stent placement and/or acute coronary syndrome) have a history of allergy to aspirin. We present a case of catastrophic early drug eluting stents thrombosis in a 79-year-old Italian woman with aspirin hypersensitivity.     

Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation.

BACKGROUND: Stent fracture is one of the possible causes of restenosis after sirolimus-eluting stents (SES) implantation. The aim of our study was to evaluate the prevalence and clinical impact of coronary stent fracture after SES implantation. METHODS: From our prospective institutional database, 280 patients were treated solely with SES from August 2004 to June 2005. Among the 280 patients, 256 patients with a total of 307 lesions underwent follow-up angiography on an average of 240 days after the procedure. RESULTS: Stent fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent fracture, five were located in the right coronary artery (RCA), two in the saphenous vein (SV) graft, and one in the left anterior descending coronary artery. The stent fractures were all in the locations that served as hinges during vessel movement in the cardiac contraction cycle. Seven of the eight stent fractures were adjacent to the edge of previously implanted or overlapped stent. Significant multivariate predictors of stent fracture were SV graft location (Odds ratio 35.88; 95% confidence interval 2.73-471.6, P = 0.006), implanted stent length (Odds ratio 1.04; 95% confidence interval 1.01-1.07, P = 0.02), and RCA location (Odds ratio 10.00; 95% confidence interval 1.11-89.67, P = 0.04). In-stent binary restenosis rate was 37.5% and target lesion repeat revascularization rate was 50.0% in patients with stent fracture. CONCLUSIONS: Stent fracture was likely to be affected by mechanical stress provoked by rigid structures and hinge points. Stent fracture might be associated with the high incidence of target lesion revascularization.     

Stent thrombosis after complex multivessel stenting in an elderly patient

We report a challenging case in terms of procedural difficulty as well as long‐term patency. Multivessel stenting procedures for long subtotal occlusions in the right coronary artery (RCA) and left anterior descending coronary artery (LAD) were successfully performed in an 84‐year‐old female who had complications of severe left ventricular dysfunction and a recent history of gastric ulcer bleeding. Two bare‐metal stents were successfully deployed in the mid and distal RCA. A drug‐eluting stent could only be deployed in the proximal RCA. Two drug‐eluting stents were deployed in the proximal LAD and LMT. Late stent thrombosis in the proximal RCA occurred about 3 months later. We speculated that a lack of aspirin and bare metal stent restenosis were the reasons for the late stent thrombosis. This case was very challenging in terms of balancing the risk of ischemia and bleeding after coronary stent deployment. © 2010 Wiley‐Liss, Inc.     

Current Status of Drug‐Eluting Stents

First‐generation drug‐eluting stents (DES) with controlled release of sirolimus or paclitaxel from durable polymers compared with bare‐metal stents have been consistently shown to reduce the risk of repeat revascularization procedures due to restenosis. The superior efficacy was found across a wide range of patients and lesion subsets and persisted up to 5 years whereas similar outcomes have been observed in terms of death and myocardial infarction. Newer generation DES have been developed with the goal to further improve upon the safety profile of first‐generation DES while maintaining efficacy. These platforms include DES with improved and more biocompatible durable polymers, DES using bioabsorbable polymers for drug release, DES with polymer‐free drug release, and fully bioabsorbable DES. Newer generation DES with durable polymers such as zotarolimus‐eluting or everolimus‐eluting XIENCE V stents have been directly compared with first‐generation DES. Most recent results of large scale clinical trials are encouraging in terms of similar or increased efficacy while improving safety by reducing the rates of myocardial infarctions and stent thrombosis. DES using biodegradable polymers for drug release represent the next technological modification and preliminary results are favorable and demonstrate similar angiographic and clinical efficacy as first‐generation DES, but only longer term follow‐up and investigation in larger patient cohorts will determine whether their use is associated with improved long‐term safety. Fully bioabsorbable stents represent another innovative approach. Whether this innovative concept will enter into clinical routine remains yet to be determined.     

药物洗脱支架置入后血栓形成的原因分析

目的探讨药物洗脱支架置入后血栓形成的发生率以及血栓形成的原因。方法本研究为单中心药物洗脱支架的注册研究,自2001年12月至2005年12月共计3345例冠心病患者接受了药物洗脱支架的治疗,其中使用雷帕霉素洗脱支架（SES）2165例,使用紫杉醇洗脱支架（PES）1180例,完成10个月临床随访为2296例;所有患者均同时口服阿司匹林和氯吡格雷至少9个月。结果3345例患者中9例发生急性血栓形成（O．27％）,其中7例为SES、2例为PES所致（0．32％比0．17％,P=0．637）;7例发生亚急性血栓形成（0．21％）,其中5例为SES、2例为PES所致（0．23％比0．17％,P=0．526）;急性和亚急性血栓发生率为0．48％（16／3345）;13例有晚期血栓形成,5例为SES、8例为PES所致（0．34％比0．95％,P=0．114）;4例晚期血栓形成的主要原因为提前中断抗血小板药物,既往患有心肌梗死病史,心功能差,药物洗脱支架置入后晚期发生血栓致猝死6例。结论支架置入不满意,特别是分叉病变以及支架未能完全覆盖受损伤的病变段是急性和亚急性血栓形成的主要原因;中断抗血小板药物和左心功能不全是晚期血栓形成的主要原因。