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.     

Coronary restenosis after implantation of drug-eluting stents

Randomized trials comparing drug-eluting stents (DES) with bare-metal stents have shown that the former significantly reduce the incidence of angiographic and clinical restenosis into an unprecedented low, one-digit, range. However, post-DES restenosis is not zero. Next to incomplete coverage with DES of the vessel segment injured by balloon angioplasty, factors such as stent underexpansion, stent overexpansion, and nonuniform distribution of stent struts have been associated with post-DES restenosis. Current evidence suggests that inadequate, though predominantly focal, delivery of the antiproliferative agent (sirolimus or paclitaxel) into the vessel wall is likely the common cause of post-DES restenosis. There is no consensus at present on how to treat post-DES restenosis. Long-term results reported to date on small numbers of patients undergoing interventional treatment for post-DES restenosis appear to be worse than outcomes observed after the index intervention, regardless of whether another DES was implanted or not, and warrant further study.     

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.     

Late thrombosis following treatment of in-stent restenosis with drug-eluting stents after discontinuation of antiplatelet therapy.

Drug-eluting stent usage has become commonplace for the percutaneous treatment of de novo coronary lesions, but the safety and efficacy profile for their evolving usage in restenotic lesions is largely unknown. We report three cases of angiographically confirmed drug-eluting stent thrombosis following treatment of restenotic lesions that occurred late (193, 237, and 535 days) and shortly after interruption of antiplatelet therapy. All three patients suffered ST elevation myocardial infarction, and there was one death. Further studies are necessary to better define the associated risk and ideal duration of antiplatelet therapy necessary in this cohort of patients with restenotic lesions.     

Long-term clinical outcomes of drug-eluting stents vs. bare-metal stents in Chinese geriatric patients

Background & Objective Little is known about the relative efficacies of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare-metal stents (BMS) in elderly patients. The objective of this study was to evaluate the clinical outcome for geriatric patients who received either DES or BMS. Methods From January 2002 to October 2005, 199 consecutive Chinese geriatric patients (≥ 75 years old) underwent PCI with coronary DES or BMS implantation at our institution. We analyzed the major clinical end points that included all-cause mortality, cardiovascular death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis, and bleeding complications. Results The three-year cumulative rates of all-cause mortality, cardiovascular death, and myocardial infarction were significantly lower in the DES group (6.3%, 3.6%, 5.4%) compared with the BMS group (16.2%, 11.5%, 14.9%; P < 0.05). No significant differences were found in the three-year cumulative rate for target lesion revascularization (6.3% vs. 4.6%, P = 0.61) or stent thrombosis (3.6% vs. 2.3%, P = 0.70). Likewise, there were no statistically significant differences in the cumulative rate for intracranial hemorrhage, or major and minor hemorrhage at three years. Conclusions DES-based PCI was associated with a significant reduction in the three-year cumulative rate of all-cause mortality, cardiovascular death, and myocardial infarction compared with BMS, without increased risk of TLR, stent thrombosis, or bleeding complications at three years in this group of Chinese geriatric patients.     

Long-term outcomes of drug-eluting stents versus bare-metal stents in large coronary arteries

Background

Long-term (> 3 years) outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in large coronary arteries were not conclusive. In addition, large coronary vessels were defined using a wide size range (≥ 3.0 mm) in previous studies. The aim of this study was to assess the long-term efficacy of DES versus BMS in subgroups of different vessel sizes.

Methods

A total of 1096 patients (1342 lesions) who underwent either DES or BMS implantation in large coronary vessels was followed for a mean duration of 4.5 years. Patients were divided into 4 subgroups by the reference vessel diameters (Q1: 3.0–3.25 mm, Q2: 3.26–3.50 mm, Q3: 3.51–3.75 mm, and Q4: 3.76–4.50 mm). The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, target vessel revascularization, and stent thrombosis. The propensity score-adjusted Cox regression method was applied.

Results

In the 3 subgroups with smaller vessel sizes, the adjusted risk of MACE in DES recipients was reduced by 82% in Q1 (hazard ratio [HR]: 0.18, 95% confidence interval [CI]: 0.09–0.38), 49% in Q2 (HR: 0.51, 95% CI: 0.26–0.98), and 67% in Q3 (HR: 0.33, 95% CI: 0.15–0.73). However, in the largest vessel subgroup (> 3.75 mm), all clinical outcomes were not significantly different irrespective of the stent type used.

Conclusions

The incidence of MACE in 3.0–3.75 mm vessels was significantly reduced by the use of DES than by the use of BMS during a long-term follow-up. However, DES lost its benefit in > 3.75 mm vessels.     

Predictors of restenosis after placement of drug-eluting stents in one or more coronary arteries

Although drug-eluting stents (DESs) have been increasingly used in a wide variety of clinical and anatomic situations, limited data are available regarding the predictors of DES failure in unselected lesions. We investigated the incidence and predictors of restenosis after implantation of DESs in routine clinical practice. A total of 1,795 consecutive patients underwent successful implantation of sirolimus-eluting (1,374 patients, 1,788 lesions) or paclitaxel-eluting (421 patients, 517 lesions) stents. Of the 1,743 eligible patients (2,221 lesions), follow-up angiography at 6 months was obtained for 1,228 patients (70.5%, 1,577 lesions). All data were prospectively recorded and analyzed to predict the occurrence of restenosis, defined as a diameter stenosis of > or =50%. Restenosis was documented in 125 patients with 138 lesions (8.8%), and target lesion revascularization was required in 70 patients with 82 lesions (5.2%). The pattern of restenosis was 85 focal (62%), 29 diffuse (21%), 11 diffuse proliferative (8%), and 13 total (9%). Lesion length, stent length, postintervention minimal lumen diameter, preintervention minimal lumen diameter, reference artery size, complex lesions, and use of a paclitaxel-eluting stent were univariate predictors of restenosis. Multivariate analysis showed that the use of a paclitaxel-eluting stent (odds ratio [OR] 4.37, 95% confidence interval [CI] 2.90 to 6.58, p <0.001), postintervention minimal lumen diameter (OR 0.32, 95% CI 0.20 to 0.50, p <0.001), and lesion length (OR 1.02, 95% CI 1.01 to 1.04, p <0.001) were independent predictors of restenosis. In conclusion, the rate of restenosis after DES implantation in routine clinical practice was similar to the rate reported in clinical trials, confirming the efficacy of DES in routine clinical practice.     

药物洗脱支架术后再狭窄八例

目的分析药物洗脱支架术后再狭窄的因素.方法 2002年9月至2004年5月,8例经冠状动脉造影证实有药物洗脱支架术后再狭窄的患者入选本研究.所有患者均行血管内超声(IVUS)检查.再狭窄分为支架内再狭窄和节段内再狭窄.支架内再狭窄定义为支架内径狭窄大于50%;节段内再狭窄定义为支架近、远段5 mm内血管内径狭窄大于50%.结果 8例再狭窄患者中,5例是支架近段再狭窄,3例支架内再狭窄(其中2例是由于支架未充分扩张所致).支架置入过程中,5例曾行支架外后扩张,1例未完全覆盖病变.IVUS显示,8例均为局灶性狭窄,无一例弥漫性再狭窄.结论药物洗脱支架术后再狭窄主要与支架外血管损伤及未完全覆盖病变有关,且再狭窄主要发生在支架近段.即使发生支架内再狭窄,病变也较局限.     

Variable histological and ultrasonic characteristics of restenosis after drug-eluting stents

Bare-metal stents have undergone intense pathological and clinical examination, but histological characterization of drug-eluting stent (DES) restenosis (ISR) remains unknown. We report a series of cases (n = 6) with intravascular ultrasound (IVUS) and pathological examinations over 8 months after DES deployment. Tissue samples were obtained using atherectomy devices in 5 cases and a thrombectomy catheter in 1 case. Histology revealed not only smooth muscle cell proliferation, which correlated with homogeneous hypoechoic tissue by IVUS in one case, but also demonstrated delayed healing features such as organized fibrin deposition in 3 cases (one with homogeneous echolucent tissue by IVUS), macrophage and T-lymphocyte infiltration in others. IVUS appearance of ISR components varied from echolucent to echodense images. This report suggests a variable histological and IVUS pattern of ISR after DES implantation. Further investigations are necessary to define the potentially pro-thrombotic histological features of ISR after DES implantation, and the relationship between the molecular mechanisms of thrombosis and DES restenosis.     

Coronary in-stent restenosis in diabetic patients after implantation of sirolimus or paclitaxel drug-eluting coronary stents

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no difference in the rate of restenosis with sirolimus-(n=8) compared with paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.     

Stent thrombosis and drug-eluting stents

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis.Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES.     

In-stent restenosis and thrombosis 41 months after drug-eluting stent implantation

Evidence indicates that very late stent thrombosis (> 1 year) occurs more frequently in drug-eluting stents than in bare metal stents after discontinuation of clopidogrel. We present a case of an 83 year old man with an LAD in-stent thrombosis 41 months after stenting with a sirolimus-eluting stent in whom clopidogrel was discontinued after 6 months based on these days' guidelines. In-stent thrombus was aspirated and intracoronary ultrasound (ICUS) showed significant in-stent restenosis which had narrowed the minimal lumen diameter by 1 mm. The lesion was stented with a bare metal stent. The patient was discharged after recovery and had no recurrence of stent thrombosis in one month follow-up. We recommended indefinite dual antiplatelet therapy with aspirin and clopidogrel.     

Update on drug-eluting stents for prevention of restenosis

Despite the success of coronary stent implantations in the last decade, in-stent restenosis due to neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury and mainly consists of proliferation of smooth muscle cells and deposition of extracellular matrix. Recently, local drug delivery has been advocated as a potential strategy to prevent in-stent restenosis. Unprecedented results have been obtained in early clinical studies on sirolimus-eluting and paclitaxel-eluting stents. Trials using various pharmaceutical coatings on different coronary stents are ongoing. More types of drug-eluting stents are expected on the market in the near future. Meanwhile, the evaluation of drug-eluting stents is entering the second phase in which the safety and efficacy in more complex lesion subsets and different clinical presentations are being investigated. Results including cost-benefit analyses are expected to have a tremendous impact on the practice of interventional cardiology in the next decade.