Stent thrombosis of drug eluting stent: pathological perspective

Although, the first-generation drug eluting stents (DES) have significantly reduced rates of restenosis compared to bare metal stents (BMS), an increased risk of late stent thrombosis (LST) has emerged as a major concern. Pathologic studies of patients dying from late DES thrombosis demonstrates delayed arterial healing characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. However, recent thorough investigations revealed additional mechanisms of stent thrombosis such as hypersensitivity reaction, excessive fibrin deposit with malapposition, or neoatherosclerosis, which are associated with device-specific components and the majority of very late stent thrombosis is likely associated with these abnormal vascular responses. Therefore, although the incidence of stent thrombosis following DES implantation is similar in each period, the underlying mechanisms of this complication may vary. In the current review, the mechanisms of stent thrombosis in the DES era will be discussed using the data from autopsy studies that have been published.     

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。     

Stent thrombosis following drug-eluting stent implantation. A single-center experience

BACKGROUND: The risk of stent thrombosis (ST) following drug-eluting stent (DES) implantation may extend beyond the initial period after successful implantation. METHODS: We evaluated the incidence, timing, and clinical outcomes of patients who presented with DES-related early (30 days) angiographic ST. Between 1/2004 and 9/2006, a total of 1339 patients underwent DES implantation (90% using Cypher stents) at our institution. Dual antiplatelet therapy was recommended for 3 to 12 months. Clinical follow-up was obtained and adjudicated at 1 and 6 months following any ST event. RESULTS: We identified eight patients (0.6% of the total patients treated with DES) with definite ST. Their mean age was 67+/-13 years. Six patients (75%) were male and 37.5% (3/8) had diabetes. Acute myocardial infarction (AMI) was the clinical presentation in 87.5% of patients. Time to ST was 4 days in two (25%) of eight patients. The other six patients (75%) had late ST (>30 days). The median time to late ST was 480 days (range: 90-1080 days). Two patients had recurrent events of late ST. All cases of late ST, except one, occurred after clopidogrel treatment was discontinued. Median time from clopidogrel withdrawal to late ST was 18 months (range: 0.5-35 months). At 6 months' follow-up from the time of ST, the subsequent major adverse cardiac event (MACE) rate (including death, re-infarction, recurrent ST or need for emergent CABG) was 62.5% and overall and/or cardiac mortality rate was 12.5%. CONCLUSION: We found that ST occurred infrequently (0.6%) and the majority (75%) of patients developed ST late (>30 days) and beyond the period recommended for dual anti-platelet pharmacotherapy. Major adverse cardiac events following ST are substantial at 6 months and thus deserve careful clinical attention.     

药物洗脱支架置入术的长期随访

目的:了解药物洗脱支架(DES)置入术的长期疗效.方法:收集255例DES置入及258例金属裸支架(BMS)置入患者的临床资料并进行长期临床随访,记录2组患者在随访时主要心血管不良事件(MACE)的发生情况.结果:与BMS组比较,DES组心绞痛再发率(6.27%:17.05%,P＜0.05)、MACE发生率(3.92%:10.47%,P＜0.05)及因心脏病住院率(5.29%:15.19%,P＜0.01)明显减少,而在晚期支架血栓形成、全因性死亡、非致死性心肌梗死及恶性肿瘤方面,2组相比差异无统计学意义.经校正了不匹配因素后发现应用BMS与心绞痛再发(r＝0.084 9,P＝0.048)、心因性死亡(r＝0.098 2,P＝0.027)、MACE(r＝0.093 7,P＝0.035)及因心脏病住院(r＝0.090 8,P＝0.041)的发生呈正相关.结论:与BMS相比,DES可减少心绞痛再发及MACE,而不增加晚期支架血栓形成及全因性死亡.     

Stent thrombosis with an aneurysm 7 years after a drug eluting stent implantation

We report a case of very late stent thrombosis 7 years post sirolimus eluting stent implantation presenting as ST elevation MI while on dual antiplatelet therapy. Angiography revealed an aneurysm at the proximal end of the stent. The patient was managed successfully by primary percutaneous coronary intervention (PCI) with adjunct thrombus aspiration and intracoronary abciximab administration followed by deploying a mesh-covered stent MGuard. This very late complication is a rare presentation after a drug illuting stent (DES).     

国产西罗莫司洗脱支架治疗冠心病的近远期疗效

目的评价国产西罗莫司洗脱支架（Firebird）在冠心病患者中应用的近、远期疗效。方法2003年11月至2005年1月共410例冠心病患者（460处病变）置入Firebird支架501个。所有患者术前、术后均给予足量抗血小板药物,通过门诊或电话随访,部分患者进行了冠状动脉造影复查来评估Firebird支架在国人冠心病治疗中的临床疗效。结果手术成功率99．5％,术中有1例支架内血栓形成;术后住院期间有1例猝死,主要不良心脏事件（包括死亡、非致死性心肌梗死和靶病变血管重建术）发生率为0．2％（1／410）;376例患者完成随访,随访率91．7％,平均随访时间（12．8±3．2）个月,死亡3例,非致死性心肌梗死4例,11例进行了再次靶病变重建术,主要不良心脏事件发生率为4．3％（16／376）,支架内血栓发生率1．1％（4／376）。102例（122处病变）进行冠状动脉造影复查,支架内再狭窄率占所有随访患者的2．9％（12／418）,占所有造影复查的9．8％（12／122）。结论Firebird支架在国人冠心病介入治疗中的应用是安全和有效的,但尚需大规模的随机对照试验来评价。     

Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials

Purpose

Drug-eluting stents are commonly used for percutaneous coronary intervention. Despite excellent clinical efficacy, the association between drug-eluting stents and the risk for late thrombosis remains imprecisely defined.

Methods

We performed a meta-analysis on 14 contemporary clinical trials that randomized 6675 patients to drug-eluting stents (paclitaxel or sirolimus) compared with bare metal stents. Eight of these trials have reported more than a year of clinical follow-up.

Results

The incidence of very late thrombosis (>1 year after the index procedure) was 5.0 events per 1000 drug-eluting stent patients, with no events in bare metal stent patients (risk ratio [RR] = 5.02, 95% confidence interval [CI], 1.29 to 19.52, P = .02). Among sirolimus trials, the incidence of very late thrombosis was 3.6 events per 1000 sirolimus stent patients, with no events in bare metal stent patients (RR = 3.99, 95% CI, .45 to 35.62, P = .22). The median time of late sirolimus stent thrombosis was 15.5 months, whereas with bare metal stents it was 4 months. Among paclitaxel trials, the incidence of very late thrombosis was 5.9 events per 1000 paclitaxel stent patients, with no events in bare metal stent patients (RR = 5.72, 95% CI, 1.08 to 32.45, P = .049). The median time of late paclitaxel stent thrombosis was 18 months, whereas it was 3.5 months in bare metal stent patients.

Conclusions

Although the incidence of very late stent thrombosis more than 1 year after coronary revascularization is low, drug-eluting stents appear to increase the risk for late thrombosis. Although more of this risk was seen with paclitaxel stents, it remains possible that sirolimus stents similarly increase the risk for late thrombosis compared with bare metal stents.     

药物洗脱支架对稳定冠心病患者血浆B型脑利钠肽的影响

目的:初步探讨稳定型冠心病(CAD)患者静脉血浆B型利钠肽(BNP)水平在长期药物洗脱支架(DES)植入后的变化以及基线BNP水平与临床事件的关系。方法:研究入选了88例稳定CAD患者,均经冠脉造影(CAG)证实。以微粒子酶免分析法(化学发光法)测定所有入选者血BNP浓度。其中29例在DES植入后进行了CAG复查和BNP测定。随访1年时的死亡、非致死性急性冠脉综合征(ACS)、再次PCI、再次心血管原因入院等不良心血管事件。结果:BNP水平:冠脉造影Gensini评分33组(44例)的显著高于Gensini评分≤33组(44例)的,P=0.0468。DES植入8月后BNP水平明显降低[(230.43±48.81)∶(149.33±17.49)pg/ml,P=0.0382]。平均随访10.5个月,BNP高水平组死亡、非致死性ACS、再入院和再次PCI率均显著高于低水平组(P=0.001)。结论:稳定CAD病变程度越重,BNP水平越高,而DES植入8月后BNP水平降低可能反映了心功能的改善;基线BNP水平对稳定CAD心血管事件可能有重要预测价值。     

冠状动脉支架内血栓形成(附5例报告)

目的分析冠状动脉支架内血栓形成的临床相关因素。方法回顾性分析571例冠状动脉支架治疗中的5例支架内血栓形成患者的临床资料、冠状动脉造影结果以及围手术期的抗血栓治疗等相关因素。结果5例急性冠状动脉综合征患者6处靶病变支架内血栓形成,其中3处为C型病变,4处置入药物洗脱支架。支架内血栓形成的原因:1处为支架不完全贴壁,2处支架不能完全覆盖病变,2例为患者抗血栓治疗不充分。结论冠状动脉支架内血栓形成可能与下列因素相关:(1)急性冠状动脉综合征;(2)长病变,支架贴壁不好,支架没有完全覆盖病变,使用药物涂层支架;(3)不充分的抗血栓治疗。     

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.     

药物涂层支架晚期血栓形成相关因素的分析

目的 探讨药物涂层支架（DES）晚期血栓形成的相关因素.方法 分别纳入我院2008年1月～2013年1月DES置入术后发生晚期血栓患者30例（血栓组）和置入DES 1年以上未发生支架内血栓患者30例（对照组）,通过64SCT冠状动脉成像观测支架贴壁情况、支架置入部位个数及长度与直径,采集病史分析晚期血栓的危险因素.结果 与对照组相比,血栓组支架贴壁不良发生率（60.0%vs.10.0%）、采用挤压支架技术（crush技术）比例（36.7% vs.13.3%）、分叉病变发生率（43.3% vs.16.7%）、多支架（＞4）置入比例（33.3% vs.0）均较高;支架平均长度较长[（39.2±20）mm vs.（21.7±7）mm],同时支架平均直径也较大[（3.0±0.5）mm vs.（2.5±0.5）mm],差异均有统计学意义（P＜0.05）;另外,血栓组合并左室射血分数减低、糖尿病、肾功能不全及过早停用双重抗血小板治疗的发生率明显高于正常组,有统计学差异（P＜0.05）.结论 DES晚期血栓形成与多种因素有关,包括复杂病变、置入支架过多、过长等,同时还与糖尿病、肾功能不全、抗凝不足等具有相关性.     

替罗非班对复杂冠脉病变植入药物洗脱支架后亚急性血栓的影响

目的评价替罗非班对冠脉复杂病变介入治疗的安全性及对药物洗脱支架内亚急性血栓的影响。方法回顾性分析自2005年1月至2008年12月连续在解放军总医院老年心血管病研究所住院并行冠脉介入治疗的复杂冠脉病变患者289例,根据围手术期替罗非班使用率的多少分为第一阶段（即使用率较少组）171例和第二阶段（即使用率较多组）118例,分别记录两个不同阶段患者的临床特征、冠脉病变情况、支架植入情况、替罗非班使用率、出血并发症及亚急性血栓发生情况,观察并分析替罗非班对复杂冠脉病变行介入治疗的安全性及对支架内亚急性血栓形成的影响情况。结果两个阶段的冠心病患者的临床资料无统计学差异,两个阶段冠脉病变为B2和C型病变的患者分别为108、63例比78、40例,无统计学差异,两个阶段平均植入支架的数量分别为（3.1±1.3）枚和（2.9±1.2）枚,平均植入支架的总长度分别为（34.4±14.3）mm和（36.5±16.3）mm,均无统计学差异。两个阶段替罗非班使用率分别为15.2%比62.7%,有显著性差异。两个阶段出血并发症的发生率分别为4.67%和4.23%,无统计学差异。两个阶段支架内亚急性血栓的发生率分别为1.75%和0%,无统计学差异,但有减少的趋势。结论复杂冠脉病变植入药物洗脱支架的围手术期使用替罗非班是安全的,且降低了支架内亚急性血栓发生的趋势。     

Stent thrombosis and platelet reactivity

Stent thrombosis (ST) is a rare but potentially life-threatening event that can occur following percutaneous coronary intervention (PCI) with stent implantation. Several factors related to the procedure or patient features can favor thrombus formation and development of ST. Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 inhibitors is the cornerstone of strategy for reducing incidence of ST. Two main causes of DAPT failure have been identified: the inappropriately premature antiplatelet therapy discontinuation and hyporesponsiveness to antiplatelet drugs. There is growing evidence that a residual high on treatment platelet reactivity (HPR) is associated with increased risk of thrombotic complications after PCI, including ST. In recent years numerous platelet function tests were developed and some of these have been extensively used in clinical studies to evaluate residual platelet reactivity, after antiplatelet drugs administration. The identification of patients with HPR is fundamental for optimization of antiplatelet treatment. Nevertheless first studies suggested that achieving a more intense platelet inhibition, switching from standard to an intensified treatment regimen on the basis of platelet reactivity, has failed to show any benefit in terms of clinical events. Certainly individualized pharmacological treatment of patients undergoing PCI remains one of the most important objectives in order to prevent serious PCI complications, such us ST.     

国产药物洗脱支架治疗冠心病九个月随访结果

目的：观察国产药物洗脱支架择期治疗冠心病的临床近、远期疗效。方法：2004年8月至2006年2月择期接受Firebird支架（雷帕霉素洗脱支架）治疗的265例冠心病患者，368支病变血管的401处相关病变置入421枚Firebird支架，随访9个月以上。结果：支架植入成功率100％，30天、6个月、9个月的严重心脏不良事件（包括死亡、再发心肌梗死、靶血管再成形等）分别为1．13％、1．51％、3．77％，血栓形成发生率为0，造影随访率32．01％，9个月的支架内再狭窄率为3．53％。结论：国产药物洗脱支架有良好的临床近、远期疗效。     

雷帕霉素洗脱支架治疗多支冠状动脉病变的临床研究

目的:探讨多支冠状动脉病变患者置入雷帕霉素洗脱支架(Cypher支架)预防再狭窄的疗效及安全性。方法:2001年12月-2004年5月连续725例接受多支冠状动脉支架置入术的冠心病患者,剔除急性心肌梗死及再次血运重建患者。Cypher支架组187例,普通金属支架(普通支架)组538例。比较两组支架术后的近期及远期结果。结果:除糖尿病患者比例在Cypher支架组较高外,两组患者冠心病危险因素、心功能、冠状动脉病变严重程度、介入手术成功率及并发症发生率均无显著差异。690例患者平均随访(18.8±11.7)个月,Cypher支架组和普通支架组造影随访率分别为52.4%vs58.2%(P>0.05)。尽管Cypher支架组患者冠心病危险因素多、平均年龄63.5岁、不稳定性心绞痛占66.3%、糖尿病占41.6%、3支血管病变占57.8%、B2/C型复杂病变占86.2%,但造影复查再狭窄率和主要不良心脏事件(MACE)发生率均明显低于普通支架组(3.1%vs16.6%,5.5%vs16.7%,P均<0.01),心功能改善率高于普通支架组(63.1%vs30.6%,P<0.01)。两组完全血运重建率无显著差异(81.3%vs86.8%,P>0.05),但发生MACE的患者中,Cypher支架组不完全血运重建者比例高于普通支架组(60.0%vs23.5%,P<0.05);两组发生MACE的患者中完全血运重建患者比例均低于本组总的完全血运重建率(Cypher支架组:40.0%     

Comparison of one-year clinical outcomes with paclitaxel-eluting stents versus bare metal stents in everyday practice

BACKGROUND:

In randomized trials, paclitaxel-eluting stents (PES) have been shown to be superior to bare metal stents (BMS) in reducing restenosis. However, the effectiveness of PES in patients treated during routine practice has not been fully established.

METHODS:

A retrospective comparison of PES with BMS in consecutive patients undergoing percutaneous coronary intervention (PCI) from April 2003 to March 2004 was conducted. Outcomes included the composite of death, myocardial infarction and target lesion revascularization (TLR) at one year, as well as stent thrombosis.

RESULTS:

A total of 512 patients were treated with PES, and 722 patients were treated with BMS. Patients in the PES group were more likely to receive stents that were 20 mm in length or longer (52.2% versus 33.3%, P<0.0001), 2.5 mm in diameter or smaller (29.1% versus 12.5%, P<0.0001) and implanted in bifurcation positions (15.4% versus 11.6%, P=0.02). At one year, the composite outcome of death, myocardial infarction and TLR was 6.1% in the PES group compared with 10.8% in the BMS group (P=0.004). The one-year rate of stent thrombosis was 0.59% in the PES group compared with 0.28% in the BMS group (P=0.4).

CONCLUSIONS:

Despite being used in higher-risk lesions, there was a lower rate of major cardiac events at one year in patients treated with PES, primarily driven by the reduction in TLR. Thus, the experience with PES in contemporary practice applied to a broader population appears to be consistent with the results reported in randomized trials.     

Relationship between symptom-onset-to-balloon time and long-term mortality in patients with acute myocardial infarction treated with drug-eluting stents

Background

Time from hospital arrival to reperfusion in ST-segment elevation myocardial infarction (STEMI) has been predictive of in-hospital mortality. The purpose of this study was to evaluate the relationship between symptom-onset-to-balloon time and long-term mortality in patients with STEMI in the drug-eluting stent (DES) era.

Methods

A series of 393 patients with STEMI treated with DES from 2005 to 2007 was stratified according to risk profile and preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow grade, and clinical, angiographic, and follow-up data were collected.

Results

A total of 98 (24.9%) low-risk patients and 295 (75.1%) non-low-risk patients were identified. Three-year mortality rate was 3.1% for low-risk patients and 10.2% for non-low-risk patients (p = 0.034), respectively; however it did not differ according to symptom-onset-to-balloon time in either low-risk (p = 0.333) or non-low-risk patients (p = 0.881). Similarly, symptom-onset-to-balloon time and mortality were not related to preprocedural TIMI flow (p = 0.474 for TIMI 0–1; p = 0.428 for TIMI 2–3). In multivariate analysis, final TIMI flow 0–2, systolic blood pressure <100 mmHg at admission, age ≥70 years, anterior infarction, C-reactive protein level, and peak creatine kinase myocardial band isoenzyme level were identified as independent predictors of 3-year mortality while symptom-onset-to-balloon time and preprocedural TIMI flow were not.

Conclusions

In STEMI patients treated with DES, symptom-onset-to-balloon time does not affect long-term outcomes even in individuals at non-low risk and with poor preprocedural TIMI flow grade.