Simultaneous late stent thrombosis in two coronary arteries following drug-eluting stent implantation

Late stent thrombosis has emerged as an infrequent but serious complication of drug-eluting stent (DES) implantation. Premature cessation of dual antiplatelet therapy is the most common risk factor for its occurrence. In the era of multivessel stenting with DES, there is a potential for multivessel late stent thrombosis following cessation of dual antiplatelet therapy. We present a rare case of a patient who sustained simultaneous late stent thromboses in DESs implanted in two coronary arteries as a result of premature cessation of dual antiplatelet therapy.     

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.     

Double jeopardy: balance between bleeding and stent thrombosis with prolonged dual antiplatelet therapy after drug-eluting stent implantation

Prolonged dual antiplatelet therapy with aspirin and clopidogrel is mandatory after drug-eluting stent (DES) implantation because of potential increase risk of stent thrombosis compared to bare-metal stents. As more DES are being implanted, many of these patients will undergo non-cardiac surgery whilst on antiplatelet therapy. The optimal management of perioperative antiplatelet therapy is not well established. The risk of excessive bleeding associated with antiplatelet therapy needs to be balanced against the risk of stent thrombosis with interruption of antiplatelet therapy on a case-to-case basis.     

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.     

The lack of endothelization after drug-eluting stent implantation as a cause of fatal late stent thrombosis

The authors present a fatal case of late thrombosis of paclitaxel-eluting stent implanted in the left main stem occurring 6 months after the procedure and 3 weeks after the cessation of clopidogrel. An autopsy has shown the lack of endothelization of deployed stent.     

Safety and efficacy of drug-eluting stents and bare metal stents in acute coronary syndrome

Compared with medical therapy, percutaneous coronary intervention has been shown to reduce the rates of death and recurrent ischemia in patients presenting with acute coronary syndromes (ACS). In the current interventional era, both drug-eluting stents (DES) and bare-metal stents (BMS) have been widely used, despite the fact that the use of DES in the context of ACS was initially an “off-label” indication and that ACS has been associated with stent thrombosis (ST). In contrast to the wealth of data available for the use of DES in patients with ST-elevation myocardial infarction, data regarding the performance of DES in non–ST-elevation ACS is restricted to a handful of registries with conflicting data. The aim of this review was to summarize the safety and efficacy of DES in the entire spectrum of ACS.     

Comparison of incidence and angiography patterns in definite thrombosis between drug-eluting and bare-metal stents

Stent thrombosis is a feared complication of percutaneous coronary intervention due to its catastrophic consequences. We analysed the incidence of angiographically-confirmed thrombosis in 5011 consecutive patients treated with drug-eluting stents or bare-metal stents. Although the incidence of thrombosis was similar between the two groups (0.8%), angiographically-documented late thrombosis was a relatively unusual complication after implantation of either stent, though it was more common with drug-eluting stents than bare-metal stents (0.25 vs. 0.06%, P = .03).     

Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS)

Background

This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial.

Methods

124 patients with definite ST were assessed by IVUS during the acute ST event. The study was conducted in 15 high-volume percutaneous coronary intervention -centers in the Nordic–Baltic countries.

Results

In early or late ST there were no differences in ISA between DES and BMS. In very late ST, ISA was a more frequent finding in DES than in BMS (52% vs.16%; p = 0.005) and the maximum ISA area was larger in DES compared to BMS (1.1 ± 2.3 mm² vs. 0.1 ± 0.5 mm²; p = 0.004). Further, ISA was more prevalent in sirolimus-eluting than in paclitaxel-eluting stents (58% vs. 37%; p = 0.02). Stent fractures were found both in DES (16%) and BMS (24%); p = 0.28, and not related to time of stent thrombosis occurrence. For stents with nominal diameters ≥ 2.75 mm, 38% of the DES and 22% of the BMS had a minimum stent area of less than 5 mm²; p = 0.14.

Conclusions

Very late stent thrombosis was more prevalent and associated with more extensive ISA in DES than in BMS treated patients. Stent fracture was a common finding in ST after DES and BMS implantation.     

Late coronary stent thrombosis: early vs. late stent thrombosis in the stent era.

The incidence of coronary stent thrombosis is < 1%-2% in recent studies, with the highest-risk period considered to be the first 30 days following stent implantation. Recently, stent thrombosis after 30 days has been reported in patients undergoing brachytherapy with stenting. We reviewed the incidence of stent thrombosis causing myocardial infarction in nonbrachytherapy patients at our institution between 1 January 1996 and 30 November 1999. A case control methodology was employed with a 1:3 ratio of stent thrombosis to control patients. Of 1,191 patients undergoing coronary stenting, acute (< 24 hr) plus subacute (1-30 days) stent thrombosis occurred in 0.92% (11 of 1,191 patients). A further 0.76% (9 of 1,191 patients) developed late stent thrombosis after 30 days. There were no clinical or angiographic features at the time of the initial procedure that were associated with stent thrombosis as an entire group compared with control group, but early (acute and subacute) stent thrombosis patients had a smaller final stent minimal lumen diameter and longer stent length compared with patients who had late stent thrombosis or controls. Late stent thrombosis occurs in nonbrachytherapy patients and is almost as frequent as early stent thrombosis. Further studies are required to determine whether longer-term poststent pharmacological treatment may decrease or prevent this complication.     

Acute myocardial infarction late following stent implantation: Incidence, mechanisms and clinical presentation

Acute myocardial infarction (AMI) can occur late following stent implantation with an incidence up to > 6% at 3-4 years, with no difference between DES and BMS. AMI can originate either from the stented site or from disease progression at nonstented sites. Restenosis, against previous thoughts, can lead to AMI. Stent thrombosis occurs with similar overall frequency following DES and BMS implantations, although a higher very late stent thrombosis with DES has been observed. Dissimilar mechanisms between BMS and DES thrombosis are very likely, with impaired neointimal healing being the rule for DES but the exemption for BMS. The use of invasive imaging techniques is useful in elucidating the involved mechanism. Disease progression is a particularly important cause of AMI late post stenting. The angiographic study depicted stent failure and disease progression equally implicated in the AMI late post stenting. When the AMI underlying mechanism is stent thrombosis, it usually occurs earlier and more frequently presented as STEMI compared to the other causes of AMI. The AMI caused by restenosis is more often presented as nonSTEMI, while disease progression leads to AMI later than the other causes. Further research should address equally not only the stent related inadequacies but also disease progression as causes of the future AMI. Angiographic follow-up and intracoronary imaging seem the most appropriate methods to define the exact pathophysiologic mechanism responsible for the AMI post stenting.     

Recurrent very late drug-eluting stent thrombosis

In-stent thrombosis is a severe and potentially fatal event. The incidence of this pathological process does not differ significantly after implantation of either bare metal or drug-eluting stents (DESs) in the first month after intervention, but stent thrombosis (ST) continues to occur over a long period of time after implantation of DESs, a phenomenon known as late and very late ST. Multiple predictors of late ST have been identified, and among others, patient's adherence to medical therapy as well as an optimal interventional technique of stent implantation emerge as crucial variables. Scarce data is available about the occurrence of recurrent very late ST. We report three cases of recurrent very late thrombosis of first generation DESs in middle-aged patients with different degrees of coronary artery disease, presenting with acute myocardial infarction.     

Very late drug-eluting stent thrombosis after nonsteroidal anti-inflammatory drug treatment despite dual antiplatelet therapy

BACKGROUND:

Drug-eluting coronary stent implantation emerged as a safe and effective therapeutic approach by preventing coronary restenosis and reducing the need for further revascularization. However, in contrast to bare metal stents, recent data suggest a unique underlying pathology, namely late coronary stent thrombosis and delayed endothelial healing.

OBJECTIVE:

To report a case of very late coronary stent thrombosis (834 days after implantation) requiring repeat urgent target-vessel revascularization. Importantly, six days before the acute coronary event, combined nonsteroidal anti-inflammatory drug therapy was initiated.

RESULTS:

Although a dual antiplatelet regimen was continuously maintained, aggregation measurements indicated only partial antiplatelet effect, which returned to the expected range when nonsteroidal anti-inflammatory drugs were omitted.

CONCLUSIONS:

The observation indicates that, even 834 days after drug-eluting stent implantation, effective combined antiplatelet therapy might be crucial in certain individuals and the possible impact of drug interactions should not be underestimated. Further efforts should focus on the challenging task of identifying patients or medical situations with prolonged, increased risk of stent thrombosis.     

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(cypherTM)在急性ST段抬高心肌梗死急诊经皮冠状动脉介入治疗中的应用

目的　探讨雷帕霉素药物洗脱支架 (cypherTM)在急性ST段抬高心肌梗死 (STEMI)急诊经皮冠状动脉介入治疗 (PCI)中应用的安全性和有效性。方法　选择 2 0 0 2年 11月至 2 0 0 4年 2月的STEMI患者 96例 ,随机分为两组 :药物洗脱支架组 ( 4 8例 )和普通支架组 ( 4 8例 ) ,所有患者均于发病12h内行急诊PCI治疗 ,一组置入cypherTM ,另一组置入普通支架。结果　 96例患者急诊PCI治疗均获得成功。 4 8支梗死相关血管 (IRA)的 4 8处罪犯病变置入 4 9枚药物洗脱支架 ,另 4 8支IRA的 4 9处病变置入 4 9枚普通支架。未发生与介入治疗有关的并发症 ,其中 1例置入cypherTM 者术后出现脑梗死 ,于第 7天死于多器官功能衰竭。药物支架组和普通支架组相比较 ,PCI后造影结果和临床结果差异均无显著性。随后对 95例病人进行了 1～ 9个月随访 (平均 4 5± 2 6个月 ) ,药物支架组患者未发生任何心血管事件 ,普通支架组有 2例发生心绞痛。结论　cypherTM 在STEMI急诊PCI中应用与普通支架一样有较强的安全性和有效性     

Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial Infarction

Background

Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain.

Objective

To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).

Methods

We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.

Results

Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02).

Conclusions

DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction.     

不同双重抗血小板治疗时间对药物洗脱支架极晚期血栓患者预后的影响

目的：分析药物洗脱支架（DES）术后发生极晚期支架内血栓（VLST）的患者接受双重抗血小板治疗（DAPT）的情况,探讨不同DAPT持续时间对患者远期预后的影响。方法2006年1月至2013年2月,首都医科大学附属北京朝阳医院心脏中心共完成3945例急诊冠状动脉造影,入选经急诊造影证实为VLST的患者。根据随访期间是否仍持续使用DAPT,将患者分为持续DAPT组和对照组。比较两组患者的临床资料、造影及介入治疗资料以及抗血小板药物治疗情况。临床主要不良心血管事件（MACE）包括随访期间的非致死性心肌梗死（MI）,再发支架内血栓（ST）,靶血管重建率（TVR）以及死亡。探讨不同DAPT持续时间对患者远期预后的影响,并分析随访期间发生MACE的预测因素。结果共计有62例VLST患者纳入研究,其中男性55例,女性7例,年龄41～82（58.6±10.2）岁。VLST距第1次DES置入时间为12.5～84（38.7±18.1）个月。住院期间脑出血死亡1例,存活的61例患者随访5～88（32.1±19.1）个月。随访期间,又有17例患者出现MACE,Kaplan-Meier生存率分析提示无事件生存率为45.1%。末次随访时,坚持持续DAPT的患者38例,其中5例（13.2%）发生MACE,事件发生率明显低于对照组（54.2%,P＝0.001）。根据是否发生MACE事件将所有患者分为两组,Cox单因素分析提示再次置入第一代DES[危害率（hazard ratio,HR）：2.69,P＝0.04]和持续DAPT（HR：0.25,P＝0.01）为远期随访中MACE相关的预测因素。而多因素Cox分析则提示仅有持续DAPT是随访期间不发生MACE的唯一预测因素（HR：0.30,95% CI：0.09～0.97,P＝0.04）。结论 DES术后VLST患者远期预后情况欠佳,事件发生率较高。坚持DAPT可能有助于减少远期不良事件的发生。     

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.