Stent thrombosis with drug-eluting stents: a re-examination of the evidence.

The excitement of drug-eluting stents and their promise for reduced restenosis rates have been tempered by recent reports of stent thrombosis. The mechanism of stent thrombosis is multifactorial but appears to be related to delayed endothelialization and healing, late stent malapposition, and antiplatelet resistance. The most important risk factor appears to be the discontinuation of dual antiplatelet therapy. The data from clinical trials suggest that drug-eluting stents are associated with increased incidence of death or myocardial infarction compared with bare metal stents at long-term follow-up, suggesting that the window of thrombotic risk with drug-eluting stents may extend far beyond that for bare metal stents. Measures to possibly decrease the incidence of stent thrombosis include improvements in antiplatelet regimens and newer generation of drug-eluting stents which have biodegradable polymers or are polymer-free. In addition, percutaneous coronary intervention with bare metal stents in patients may be helpful in those known to be intolerant or noncompliant to antiplatelet therapy, have planned procedures or surgeries, or have overwhelming risks which may require discontinuation of dual antiplatelet therapy.     

Very Late Angiographic Stent Thrombosis with Cyphertrade mark Stent Despite Being on Aspirin Therapy

Late angiographic stent thrombosis after Cyphertrade mark stent implantation has been reported to occur till approximately one year after the procedure and usually soon after the discontinuation of all antiplatelet medication.We report a case of very late stent thrombosis occurring 27 months (790 days) after stent implantation and 13 months after clopidogrel discontinuation despite being on regular aspirin. This case underlines the possible need for long-term dual antiplatelet therapy after implantation of drug-eluting stents.     

Very late stent thrombosis associated with multiple stent fractures and peri-stent aneurysm formation after sirolimus-eluting stent implantation.

Previous randomized trials have shown that drug-eluting stents (DES) are superior to bare-metal stents in reducing the need for target lesion revascularization, but safety issues with DES have recently been raised. We report a rare case of very late stent thrombosis 35 months after sirolimus-eluting stent implantation associated with delayed 5-segment stent fractures and peri-stent aneurysm formation.     

Very Late Stent Thrombosis 11 Years after Implantation of a Drug-Eluting Stent

Very late stent thrombosis is an infrequent yet potentially fatal complication associated with drug-eluting stents. We report the case of an 88-year-old man who sustained an ST-segment-elevation myocardial infarction 11 years after initial sirolimus-eluting stent implantation. Optical coherence tomograms of the lesion showed that the focal incomplete endothelialization of the stent struts was the likely cause; neointimal formation, neoatherosclerosis, and late stent malapposition might also have contributed.To our knowledge, this is the longest reported intervening period between stent insertion and the development of an acute coronary event secondary to very late stent thrombosis. The associated prognostic and therapeutic implications are considerable, because they illuminate the uncertainties surrounding the optimal duration of antiplatelet therapy in patients who have drug-eluting stents. Clinicians face challenges in treating these patients, particularly when competing medical demands necessitate the discontinuation of antiplatelet therapy. In addition to the patient''s case, we discuss factors that can contribute to very late stent thrombosis.     

支架内晚期血栓及其防治进展

早期和晚期支架内血栓给当前经皮冠状动脉介入治疗带来棘手的问题,可以导致非致命性心肌梗死和心源性死亡。晚期支架内血栓较少见但往往带来严重后果,多见于药物洗脱支架术后。支架内血栓的发生主要与支架置入技术、病变特征、双重抗血小板治疗效果、局部组织对雷帕霉素或紫杉醇等涂层药物的反应等因素有关。使用新一代药物洗脱支架可能减少晚期支架内血栓发生的风险。     

Acute ST-elevation myocardial infarction 6 years following a sirolimus-eluting stent secondary to complete stent fracture

With increasing coronary interventions, coronary stent fracture following implantation of drug-eluting stents is being commonly recognized. Though isolated strut fractures are often only incidental findings, more severe forms of stent fracture with complete transection have adverse clinical outcomes. Most such cases are reported within several months following the index angioplasty. We report an unusual presentation of late stent fracture following a sirolimus-eluting stent, presenting with acute myocardial infarction 6 years after the initial stent implantation. The various mechanisms underlying fracture of drug-eluting stents are reviewed. Because no known mechanisms were noted in our case, unknown factors may also play a role in the genesis of stent fracture. Clinicians need to be aware that such complications may present rarely, extremely late after the index procedure as an acute myocardial infarction.     

药物洗脱支架植入后靶血管的病理改变

药物洗脱支架广泛应用于冠心病的治疗,有效地减少了支架再狭窄的发生,但晚期支架内血栓形成、支架动脉瘤形成、靶血管部位超敏反应的发生等一系列的并发症逐渐被人们所重视,现探讨药物洗脱支架植入后靶血管的病理学改变.     

血管内超声在冠状动脉药物洗脱支架晚期血栓研究中的应用

药物洗脱支架与金属裸支架相比,减少了再狭窄的发生率,但其长期安全性却引起了人们的注意。支架置入30 d以后出现的晚期支架内血栓问题成为目前介入心脏病学的研究热点。晚期支架内血栓发生率低,但一旦发生后果严重。有研究显示其发生的原因可能包括动脉的延迟愈合、动脉瘤形成及支架贴壁不良等。现就血管内超声在冠状动脉药物洗脱支架晚期血栓研究中的应用进展做一评述。     

Fracture of Zotarolimus-Eluting Stent after Implantation

Drug-eluting stents were developed and approved for the reduction of in-stent restenosis. However, restenosis still occurs, and stent fracture is suggested as a cause of restenosis after implantation. Although sirolimus-eluting stents are considered to carry a high risk of fracture, the risk is also present with other drug-eluting stents. Herein, we report the case of a 78-year-old woman who received a zotarolimus-eluting stent for a bifurcation lesion of the left anterior descending coronary artery. Ten months later, she underwent coronary angiography due to angina. The angiogram revealed in-stent restenosis, with a grade IV stent fracture. After percutaneous coronary angioplasty, the patient''s clinical symptoms improved.Key words: Blood vessel prosthesis implantation/instrumentation, coronary restenosis/diagnosis/etiology/prevention & control, drug-eluting stents, drug implants/adverse effects, prosthesis failure, retreatment, stents/adverse effectsAlthough drug-eluting stents (DESs) reduce in-stent restenosis, important complications of coronary DESs are restenosis and thrombosis. Stent fractures have also been reported¹ and are considered to be possible causes of restenosis² within DESs. The sirolimus-eluting stent is reported to be prone to fracture.³ For example, there is the Cypher® stent (Cordis Corporation, a Johnson & Johnson company; Miami Lakes, Fla)—made of balloon-expandable stainless steel, a durable copolymer mixture of polyethylene-covinyl acetate and poly-u-butyl methacrylate, and sirolimus, which is a Gap 1 (G1) cell-cycle inhibitor.⁴ Other DESs are also considered to be at risk of fracture. One, the Endeavor® Sprint Zotarolimus-Eluting Coronary Stent System (Medtronic, Inc.; Minneapolis, Minn), uses a cobalt chromium stent platform; a durable, antithrombotic, phosphorylcholine-encapsulated coating; and another G1 cell-cycle inhibitor, zotarolimus.⁴ Here, we report the case of a woman who was treated with a zotarolimus-eluting stent that subsequently fractured.     

Thrombose coronaire très tardive par fracture du stent actif. Cas clinique et revue de la littérature

The superiority of drug-eluting stents in reducing the risk of in-stent restenosis compared to bare-metal stents is no longer challenged. Nevertheless, the drug-eluting stents may carry long-term risk of late and very late stent thrombosis. The promoting factors of this complication are usually divided into three chapters depending on the patient, the procedure and the stent. Indeed, the literature has reported several parameters related to the stent itself, such as its length, the malapposition, its diameter, but also more rarely the occurrence of stent fracture. We present the case of a patient admitted for myocardial infarction after a very late thrombosis of Cypher drug-eluting stent four years after its implantation and related to stent fracture.     

Recurrent late drug-eluting stent thrombosis upon discontinuation of antiplatelet therapy

Stent thrombosis is a rare but serious complication of percutaneous coronary intervention. Stent thrombosis usually occurs early after stent implantation but can occasionally occur late, especially when drug-eluting stents are used. We report a case of recurrent late paclitaxel-eluting stent thrombosis (8 and 21 months after initial stent implantation) upon discontinuation of dual antiplatelet therapy.     

Simultaneous Very Late Stent Thrombosis in Multiple Coronary Arteries

We report 2 noteworthy cases of very late stent thrombosis presenting as ST-segment-elevation myocardial infarction, with vastly different manifestations. Both patients were women who had histories of multivessel percutaneous coronary intervention with first-generation sirolimus-eluting stents, in 2005 and 2006. On the more recent occasions reported here, one underwent successful multivessel primary percutaneous coronary intervention, while the other underwent successful multivessel “plain old balloon angioplasty.” Both were discharged from the hospital with advice to stop smoking and to follow a lifelong regimen of aspirin and clopidogrel.On the basis of these two cases and our review of the current literature, we ask whether it is now prudent to recommend lifelong dual antiplatelet therapy after drug-eluting stent deployment. Moreover, in order to account for cases of stent thrombosis that occur ≥5 years after drug-eluting stent implantation, should we perhaps suggest the addition of “extremely late stent thrombosis” to the existing Academic Research Consortium classification?Key words: Aspirin, clopidogrel, coronary restenosis/etiology, coronary thrombosis/etiology, drug delivery systems/adverse effects, immunosuppressive agents, paclitaxel, platelet aggregation inhibitors/therapeutic use, sirolimus/therapeutic use, stent thrombosis, stents, drug-eluting/adverse effects, ST-elevation myocardial infarction, very late stent thrombosisStent thrombosis after percutaneous coronary intervention (PCI) remains a serious concern for both cardiologists and patients. The incidence of stent thrombosis within the first 30 days in patients randomized to receive sirolimus-eluting stents (SES) in clinical trials is reported to be no different from that in patients randomized to a control group receiving bare-metal stents.¹ Stent thrombosis has been reported as late as 17 months,² and more recently as late as 26 months, after SES implantation.³ We report 2 cases of simultaneous very late stent thrombosis in multiple coronary arteries ≥5 years after drug-eluting stent (DES) implantation, presenting as an ST-segment-elevation myocardial infarction (STEMI) despite a regimen of aspirin in patient 1 and both aspirin and clopidogrel in patient 2.     

Evolution of stents for the treatment of femoral artery lesions

Endovascular treatment and stent implantation in the superficial femoral artery have been proposed for over 20 years. However, the first experiments with stainless stents were relatively disappointing. The first improvement consisted in the introduction of nitinol self-expanding stents. This technology allowed an initial improvement of clinical performances, but the first generation of nitinol stents demonstrated a relatively high rate of fractures. Better knowledge of the femoral artery biomechanics and advances in technology allowed to propose a second generation of nitinol stents with improved flexibility, which decreased the rates of fracture. In-stent restenosis related to neointimal hyperplasia has also led to the development of new concepts to improve patency rates after stenting of the femoral artery: drug-eluting stents (coated-stents), biodegradable stents, and covered stents. These technologies will help to treat more complex lesions of the femoral artery in the future, with comparable results to those obtained with femoropopliteal bypasses, but we are still waiting for results of ongoing studies.     

Stent fracture: a new villain of the village

Stent strut fracture (SSF) may be an important complication after drug-eluting stent (DES) implantation particularly in patients undergoing sirolimus-eluting stent (SES) implantation. The occurrence of SSF at 6 to 9 months after the SES implantation, which was relatively common, resulted in a higher rate of focal in-stent restenosis. Although this angiographic unfavorable outcome did not lead to an increased risk of adverse cardiac events in the current study, we believe that large-scale prospective studies are needed to elucidate the exact pathophysiology and clinical sequela of the stent strut fracture, including bare metal stents.     

药物洗脱支架与金属裸支架内血栓发生率比较

目的:了解置入药物洗脱支架(DES)患者在经皮冠状动脉(冠脉)介入治疗(PCI)术后各期支架血栓(ST)的发生情况,并与置入金属裸支架(BMS)患者进行比较,探讨影响支架血栓发生的危险因素.方法:连续入选2001-07至2002-06和2003-07至2005-06期间接受PCI并置入支架的所有患者,共入选3 893例.随访至少2年.根据所使用支架分为DES组(n=2 930,至少置入1枚DES)和BMS组(n=963,单纯置入BMS).记录所有患者住院期和随访期内临床资料,并根据美国和欧洲学者组成的学术研究联盟(ARC)正式发表的支架血栓定义判定支架血栓事件.结果:与BMS组相比,DES组患者的平均年龄较大,而白细胞数、甘油三脂水平和空腹血糖水平较低,既往有冠脉血运重建病史者较多,但吸烟、糖尿病和ST段抬高型心肌梗死(STEMI)发生率较低;在DES组患者的冠脉病变中,多支病变、开口病变、前降支(LAD)近段病变和左主干(LM)病变发生率较高,但慢性完全闭塞性(CTO)病变所占的发生率较低,造影成功率及完全血运重建率均较高,差异均有统计学意义(P均＜0.05～0.001).两组患者PCI术后无论在住院期还是之后的随访期内,所有的不良心脑血管事件发生率均无显著差异,而支架血栓发生率在急性期、亚急性期、晚期和晚晚期均无差异(P均＞0.05).Cox回归分析结果提示,DES组患者发生支架血栓的危险因素为:氯吡格雷疗程短和冠脉多支病变(P均＜0.001);而BMS组患者发生支架血栓的危险因素为:血清肌酐值升高和合并高血压(P均＜0.05).结论:尽管DES时代患者的病变更为复杂,所置入的DES数更多,但支架血栓的发生率并不比BMS时代更高.但术后双联抗血小板治疗的疗程过短和冠脉多支病变是支架血栓发生的危险因素,应引起重视.     

药物洗脱支架:如何平衡再狭窄减少与支架内血栓

药物先脱支架通过抑制平滑肌细胞的增殖减少了支架内再狭窄,但也因此而出现了支架内血栓的不良反应,现综述其临床益处及局限性,并分析其导致支架内血栓的相习因素.     

Successful Prasugrel Therapy for Recurrent Left Main Stent Thrombosis in a Clopidogrel Hyporesponder

Stent thrombosis is a life-threatening sequela of drug-eluting stent implantation. Dual antiplatelet therapy with aspirin and thienopyridine is typically used to prevent this catastrophic event. In terms of stent thrombosis, the major concern is the variable response of patients to clopidogrel, and this has raised interest in new antiplatelet agents. We present the case of a 64-year-old woman whom we successfully treated with prasugrel after she had repeated episodes of stent thrombosis caused by a poor response to clopidogrel. This case highlights the potential role of new antiplatelet agents for patients who are undergoing drug-eluting stent implantation.     

Avances en el tratamiento mediante intervención coronaria percutánea: el stent del futuro

First generation drug-eluting stents have considerably reduced in-stent restenosis and broadened the applications of percutaneous coronary interventions for the treatment of coronary artery disease. The polymer is an integral part of drug-eluting stents in that, it controls the release of an antiproliferative drug. The main safety concern of first generation drug-eluting stents with permanent polymers—stent thrombosis—has been caused by local hypersensitivity, delayed vessel healing, and endothelial dysfunction. This has prompted the development of newer generation drug-eluting stents with biodegradable polymers or even polymer-free drug-eluting stents. Recent clinical trials have shown the safety and efficacy of drug-eluting stents with biodegradable polymer, with proven reductions in very late stent thrombosis as compared to first generation drug-eluting stents. However, the concept of using a permanent metallic prosthesis implies major drawbacks, such as the presence of a foreign material within the native coronary artery that causes vascular inflammation and neoatherosclerosis, and also impedes the restoration of the vasomotor function of the stented segment. Bioresorbable scaffolds have been introduced to overcome these limitations, since they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. This update article presents the current status of these new technologies and highlights their future perspectives in interventional cardiology.     

64层螺旋CT冠状动脉支架成像效果的影响因素

目的 探讨64层螺旋CT冠状动脉支架成像效果的影响因素.方法选取冠状动脉药物涂层金属支架植入术后行64层螺旋CT检查的病例116例,对支架部位图像质量采取半定量评价,分析支架直径、支架长度、支架材质、支架个数和钙化情况对支架部位CT图像质量的影响.结果 64层螺旋CT检出有意义支架内再狭窄的敏感度、特异度、阳性预测值、阴性预测值分别为85.7%、90.2%、60.0%、97.4%.直径2.75 mm以上支架的CT图像质量优于直径2.75 mm及以下的支架(P<0.001),非钙化病变的支架术后CT图像质量优于钙化病变(P<0.05).支架长度、支架材质和是否多支架对支架部位CT图像质量无影响.结论 64层螺旋CT能胜任冠状动脉支架术后复查.直径2.75 mm以上支架和非钙化病变的支架病例更适合用64层螺旋CT进行复查.     

New drug-eluting stents, optimizing technique, and the problem of drug-eluting stent restenosis

The development of drug-eluting stents is one of the major revolutions in the field of Interventional Cardiology. Restenosis rate has been significantly reduced, in comparison to bare metal stents. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but on the other hand must also enhance re-endothelialization, in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Currently sirolimus, paclitaxel and more recently, ABT-578-eluting stents are commercially available, but ongoing research and clinical trials will result in new stents coming to market with novel designs loaded with a variety of compounds. As drug-eluting stent implantation becomes more liberal leading to an extensive use of this technology, the problem of restenosis in drug-eluting stents will become more common. However, for the time being, little is known regarding optimal treatment of in-stent restenosis following drug-eluting stent implantation. Future research is mandatory to further clarify, whether these patients should be treated with the same drug-eluting stent, with a different drug-eluting stent or with increased doses.