Stent fracture associated with drug‐eluting stents: Clinical characteristics and implications

Objective : To evaluate the clinical characteristics and implications of stent fracture in drug‐eluting stents. Background : Approximately 2.5 million drug‐eluting stents are implanted every year worldwide. In 10 randomized controlled trials involving 2,602 patients, no incidence of stent fracture was recognized or reported. Methods : From April 2003 to December 2005, 2,728 patients underwent drug‐eluting stenting. The angiograms of all 530 patients who underwent repeat angiography were analyzed to identify the presence of stent fracture. We then documented the incidence of adverse events associated with drug‐eluting stent fracture and systematically analyzed the clinical, procedural, and structural factors, which might predispose to stent fracture. Results : Stent fracture was identified in 10 patients. None of these fractures were detectable at the time of stent placement. The median time interval from stent implantation to detection of fracture at repeat angiography was 226 days (range, 7–620 days). Adverse clinical outcomes associated with stent fracture occurred in 7 patients (6 patients had binary restenosis and 1 patient had stent thrombosis), all necessitating repeat intervention. Analysis of potential predisposing clinical, procedural, and structural factors revealed that 4 patients had excessive tortuosity in the proximal segment, and overlapping stents were used in 5 cases. All fractures occurred in sirolimus‐eluting stents. Conclusions : Stent fracture may represent a new potential mechanism of restenosis and stent thrombosis in drug‐eluting stents. Predisposing clinical and procedural factors may be vessel tortuosity and use of overlapping stents. The most important predisposing factor, however, may be stent structure, since all fractures occurred in sirolimus‐eluting stents. © 2006 Wiley‐Liss, Inc.     

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.     

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.     

In‐Stent Restenosis

The introduction of coronary stents marked a major turning point in the practice of interventional cardiology. Whereas the efficacy of balloon angioplasty was challenged both by immediate mechanical complications and by a high incidence of restenosis, coronary stents offered cardiologists a means by which to not only augment immediate procedural success, but also to reduce the incidence of restenosis following coronary intervention. However, despite technological advances and an improved understanding of the restenotic process, the overall rate of in‐stent restenosis following bare metal stent implantation remains high. Although the introduction of drug‐eluting stents has further reduced the incidence of restenosis, the “real‐world” application of drug‐eluting stents in increasingly complex lesion and patient subsets has given way to the even greater clinical challenge of managing drug‐eluting stent restenosis. Although the standard treatment of bare metal stent restenosis typically involves placement of a drug‐eluting stent, the optimal therapeutic approach to drug‐eluting stent restenosis remains less defined. The issue of in‐stent restenosis (especially following implantation of a drug‐eluting stent) remains a clinical challenge, and investigation into therapeutic options remains ongoing. As technology evolves, such investigation will likely incorporate novel approaches including drug‐coated balloons novel stent designs.     

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.     

雷帕霉素洗脱支架与紫杉醇涂层支架治疗冠状动脉复杂病变

目的评价雷帕霉素洗脱支架(CypherTM)与紫杉醇涂层支架(Taxus ExpressTM)治疗冠状动脉复杂病变(B2／C型病变)的近期和远期疗效。方法入选本研究267例,男性占68％,糖尿病占38．5％。雷帕霉素洗脱支架组169例,共植入雷帕霉素洗脱支架172条;紫杉醇涂层支架组98例,植入紫杉醇涂层支架165条。观察6个月的主要心血管事件。结果两组的临床特征相似。支架植入成功率100％,95％的病人完成6个月的随访。主要心血管事件发生率:雷帕霉素洗脱支架组5．9％(10／169),紫杉醇涂层支架组9．2％(9／98),两组差异无统计学意义(X2=1．001,P=0．317)。结论雷帕霉素洗脱支架治疗冠状动脉复杂病变疗效和安全性与紫杉醇涂层支架相似。     

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 delayed coronary stent fracture: A case report

A stent fracture is an emerging complication of the coronary stents. There are numerous risk factors for stent fractures; which include forceful exaggerated motion in the atrioventricular groove seen in right coronary artery, long stent, an ostial lesion at the point of maximum curvature in a tortuous vessel, stent over-expansion, stent overlapping with different size stents, complex lesion after stenting of a totally occluded vessel, Cypher stent and a highly mobile segment causing high mechanical stress. Furthermore, chronic stretch at specific vessel sites as bends may lead to late occurrence of fracture.Here we report a case of 40-year-old male who had two overlapping Cypher stents (3.0 × 13 mm and 2.75 × 18 mm) deployed at mid left anterior descending artery 2 years earlier presented with progressive chest pain.     

Coronary Stent Fracture: A Recently Appreciated Phenomenon with Clinical Relevance

In the stent era, in addition to restenosis, there are many important consequences deserving more attention. Firstly described in peripheral vascular interventions, it took several years for stent fracture to be known as an appreciable complication of coronary intervention. Especially with the introduction of drug eluting stents and the use of coronary stents in more complex cases, its prevalence has raised and new data have been published concerning its mechanism, predictors, diagnosis, clinical course and treatments. This review will discuss the available literature about stent fracture.     

合理看待药物洗脱支架晚期血栓问题

冠状动脉支架现广泛应用于冠心病的介入治疗中。支架内血栓是金属裸支架和药物洗脱支架的一个并发症,可导致心肌梗死或死亡。最近,药物洗脱支架引起晚期支架内血栓的问题引起人们的广泛关注。支架血栓的危险因素包括操作因素(如支架贴壁不良、置入支架的数目、支架长度及夹层)、患者及病变因素、过早停用抗血小板药物以及支架释放的药物使内皮延迟愈合等。现对支架晚期血栓的概念、发生的危险因素、防治措施等进行探讨。     

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.     

Scanning electron microscopic analysis of different drug eluting stents after failed implantation: From nearly undamaged to major damaged polymers

Background : Implantation of drug eluting stents (DES) in tortuous and/or calcified vessels is much more demanding compared with implantation of bare metal stents (BMS) due to their larger diameters. It is unknown whether drug eluting stent coatings get damaged while crossing these lesions. Methods : In 42 patients (34 male, 68.1 ± 10 years) with 45 calcified lesions (15.9 mm ± 7.9 mm), DES could not be implanted, even after predilatation. Diabetes was present in 19 patients (45 %). Sixty‐one stents were used; 19 Cypher select?, 18 Taxus Liberté?, 10 CoStar?, 5 Endeavor RX?, 4 Xience V?. 3 Janus Carbostent?, 1 Yukon Choice S?, and 1 Axxion? DES. The entire accessible surface area of these stents, in either the unexpanded and expanded state, were examined with an environmental scanning electron microscope (XL30 ESEM, Philips) to evaluate polymer or surface damage. Results : The polymers of Taxus Liberte, Cypher Select, Xience V, CoStar, and Janus DES were only slightly damaged (less than 3% of surface area), whereas the Endeavor RX Stents showed up to 20% damaged surface area. In DES without a polymer (Yukon and Axxion), it could be shown that most of the stent surface (up to 40%) were without any layer of drug. Conclusion : Placement of drug eluting stents in tortuous vessels and/or calcified lesions could cause major surface damage by scratching and scraping of the polymer or drug by the arterial wall, even before implantation. There were remarkable differences among the stents examined, only minor damage with the Cypher, Taxus Costar, Janus, and Xience V, whereas the Endeavor, the Yukon, and the Janus DES showed large areas of surface injury. © 2009 Wiley‐Liss, Inc.     

Late and very late thrombosis of drug-eluting stents: evolving concepts and perspectives

Coronary stents are the mainstay of percutaneous coronary revascularization procedures and have significantly decreased the rates of acute vessel closure and restenosis. Stent thrombosis (ST) after percutaneous coronary intervention is an uncommon and potentially catastrophic event that might manifest as myocardial infarction and sudden death. Optimization of stent implantation and dual antiplatelet therapy have markedly reduced the occurrence of this complication. Bare-metal stent (BMS) thrombosis occurs in <1% of the cases, usually within the first month after implantation. The advent of drug-eluting stents (DES) has raised concerns regarding later occurrence of ST, beyond the traditional 1-month timeframe, especially in complex lesion subsets that were excluded from randomized trials that compared BMS to DES. There is widespread controversy regarding the actual incremental risk associated with DES. Recent studies suggest a 0.5% increased long-term thrombosis risk with DES; however, the clinical significance of these events remains under debate. The degree of protection achieved by dual antiplatelet therapy and optimal duration of treatment are under investigation. Novel stent designs might potentially decrease the incidence of this event. In this review, we will describe the current knowledge of the pathophysiology of late DES thrombosis, although many aspects remain incompletely understood.     

Novel bioabsorbable salicylate‐based polymer as a drug‐eluting stent coating

Background: Permanent polymers used in current drug‐eluting stents (DES) can trigger chronic inflammation and hypersensitivity reactions, which may contribute to the increased risk of late thrombosis and rebound restenosis. Therefore, optimal polymer selection and the use of completely absorbable but biocompatible polymers are expected to minimize these risks. Objectives: We sought to evaluate a novel, potentially innately anti‐inflammatory, bioabsorbable salicylate‐based polymer as a DES coating, in a clinically relevant animal model. Methods: Four types of stents were implanted in pig coronary arteries using QCA to optimize stent apposition: bare metal stents (BMS); salicylic acid/adipic acid bioabsorbable polymer‐only coated metal stents (SA/AA); biostable polymeric sirolimus‐eluting stents (Cypher?); and metal stents coated with salicylic acid/adipic acid bioabsorbable polymer containing sirolimus (SA/AA + S). The dose density of sirolimus was 8.3 μg/mm of stent length (similar to Cypher?) with in vitro studies demonstrating elution over 30 days and complete polymer degradation in 37 days. Animals underwent angiographic restudy and were terminated at 1 month for complete histopathologic and histomorphometric analyses. Results: Both SA/AA + S and Cypher? stents had significantly lower angiographic % stenosis when compared with BMS and SA/AA polymer‐only groups (6 ± 4% and 5 ± 4% vs. 15 ± 7% and 16 ± 5%, respectively, P < 0.001). Intimal thickness was lower for SA/AA + S and Cypher? than for BMS (0.14 ± 0.06 and 0.13 ± 0.04 mm vs. 0.23 ± 0.05 mm, respectively, P < 0.001). Histologic % area stenosis was also lower for SA/AA + S and Cypher? when compared with BMS (22 ± 7% and 23 ± 6% vs. 33 ± 5%, respectively, P < 0.001). There was a strong trend toward reduced inflammatory response in the SA/AA and SA/AA + S when compared with BMS and Cypher? groups (P = 0.072). Conclusions: This study shows favorable vascular compatibility and efficacy for a novel bioabsorbable salicylate‐based polymer as a DES coating, and supports further research and development of this unique class of polymer materials for applications in cardiovascular devices. © 2008 Wiley‐Liss, Inc.     

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.     

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.     

Very late thrombosis after drug-eluting stents.

Stent thrombosis is a rare but potentially fatal complication of percutaneous treatment of coronary disease. Its occurrence after drug eluting stent (DES) placement has raised concerns, especially when it occurs late after the stent implantation. The mechanisms of late thrombosis after DES have yet to be completely understood. By means of serial angiography and intravascular (IVUS) images we described a relatively new and unusual vessel response to drug-eluting stents (e.g. huge positive remodeling in all vessel extension), leading to impressive late-acquired incomplete stent apposition and finally causing stent thrombosis and acute myocardial infarction. After describing the two cases, one after Cypher stent implantation and one after Taxus stent implantation, we briefly reviewed the literature available on stent thrombosis with special emphasis on its late occurrence.     

Cardiogenic shock caused by simultaneous subacute stent thrombosis after implantation of sirolimus-eluting stents

Stent thrombosis is a feared complication of percutaneous coronary intervention, although there is a low incidence of thrombotic events following drug-eluting stent implantation. We report a case with cardiogenic shock complicated by acute myocardial infarction due to simultaneous subacute stent thrombosis occurring 3 days after implantation of two sirolimus-eluting stents in the proximal left anterior descending artery (LAD) and in the proximal right coronary artery (RCA).     

Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.

AIM: Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2). METHODS AND RESULTS: A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52). CONCLUSION: The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.