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.     

药物洗脱支架与裸支架介入治疗冠心病的对比研究

目的比较冠心病患者应用药物洗脱支架与应用裸支架的安全性和有效性。方法回顾我院2006—2011年行冠脉支架置入术患者的随访结果,比较应用药物洗脱支架与裸支架的再狭窄率。结果应用药物洗脱支架患者的再狭窄率为8％,应用裸支架患者的再狭窄率为25％,两者相比差异有统计学意义。结论药物洗脱支架较裸支架具有更低的支架内再狭窄发生率。     

药物支架应用于冠状动脉介入治疗中的现状和前景

目前越来越多的冠状动脉性心脏病患者接受了经皮冠状动脉介入治疗,药物支架也已成为介入治疗的焦点。通过对药物支架和裸支架的比较,指出了药物支架的特点和优势,以及药物支架发展至今其安全性的争议和研究进展,并预测了其未来的发展方向。随着药物支架的不断发展,介入心脏病学必将会迎来更多的革命。药物支架取代裸支架是一种必然的趋势,可降解支架的发展则是新的里程碑。     

Efficacy and safety of drug-eluting stents in patients with acute ST-segment-elevation myocardial infarction: a meta-analysis of randomized controlled trials

We compared the efficacy and safety of drug-eluting stents with that of bare-metal stents in patients who experienced acute ST-segment-elevation myocardial infarction (STEMI) and underwent primary percutaneous coronary intervention. To do this, we performed a meta-analysis of 13 randomized controlled trials in which drug-eluting stents were compared with bare-metal stents in STEMI patients. The trials involved 6,769 patients (4,246 received drug-eluting stents and 2,523 received bare-metal stents) and follow-up periods of 6 to 48 months. In comparison with bare-metal stents, drug-eluting stents significantly reduced the incidence of major adverse cardiac events, with a risk ratio (RR) of 0.59 (95% confidence interval [CI], 0.47-0.73; P < 0.00001). Drug-eluting stents were not associated with a significant reduction in overall death (RR = 0.94; 95% CI, 0.74-1.20; P = 0.64), but were associated with significant reductions in recurrent myocardial infarction (RR = 0.76; 95% CI, 0.58-0.98; P = 0.03), target-vessel revascularization (RR = 0.47; 95% CI, 0.39-0.56; P <0.00001), and in-stent restenosis (RR = 0.32; 95% CI, 0.25-0.39; P < 0.00001). Moreover, no significant difference was found in the comparative risk of stent thrombosis (RR = 0.85; 95% CI, 0.63-1.14; P = 0.27).On the basis of risk ratio, we conclude that using drug-eluting stents in STEMI patients who undergo primary percutaneous coronary intervention is safe with regard to stent thrombosis within 48 months, and that drug-eluting stents improve clinical outcomes by reducing the risks of major adverse cardiac events, recurrent myocardial infarction, reintervention, and in-stent restenosis, compared with bare-metal stents. However, in order to investigate possible very late stent thrombosis, follow-up of these trials beyond 48 months is warranted.     

Drug-eluting stents and stent thrombosis: a cause for concern?

Drug-eluting stents, most commonly sirolimus-eluting stents and polymer-based paclitaxel-eluting stents, are now widely used during percutaneous coronary interventions, and have largely replaced bare-metal stents to treat a variety of native coronary artery and saphenous vein graft lesions. Stent thrombosis, a complication of both bare-metal and drug-eluting stents, is associated with significant morbidity and mortality including high rates of myocardial infarction and death. Recently, several studies in the literature have raised concern about increased rates of overall stent thrombosis and late stent thrombosis in drug-eluting stents in the so-called 'real world' where off-label uses of drug-eluting stents are common. Hypersensitivity reactions to the polymers used in drug-eluting stents, delayed endothelialization of the stents, and discontinuation of dual antiplatelet therapy have all been implicated in the pathophysiology of drug-eluting stents stent thrombosis. The incidence of total stent thrombosis as well as late stent thrombosis, however, does not seem to be significantly higher in drug-eluting stents than in bare-metal stents. An important risk factor for stent thrombosis in both types of stents appears to be the premature discontinuation of dual antiplatelet therapy, and physicians should educate their patients about the importance of adhering to dual antiplatelet therapy, given the dire clinical consequences of stent thrombosis.     

Drug-eluting coronary stents

The introduction and widespread use of coronary stents have been the most important advancement in the percutaneous treatment of coronary artery disease since the introduction of balloon angioplasty. Coronary artery stents reduce the rate of angiographic and clinical restenosis compared to balloon angioplasty. This angiographic restenosis was further reduced with the introduction of drug-eluting stents and hence further reduction in the frequency of major adverse cardiac events. Herein we present a comprehensive and up-to-date review about the use of drug-eluting stents in the treatment of coronary artery disease.     

药物涂层支架的研究进展

冠状动脉支架的应用极大地降低了再狭窄率,使经皮冠状动脉介入治疗有了质的飞越.冠状动脉支架发展至今已多种多样,其中药物涂层支架应用最为广泛,但药物涂层支架在降低支架内再狭窄的同时存在增加支架内血栓的风险.因此,不断改进药物支架是目前的研究热点,且药物支架向可降解支架逐渐发展.现就主要的药物涂层支架进行综述,介绍药物涂层支架的发展过程并大胆预测其发展趋势.     

Coronary artery bypass grafting following in-stent restenosis of drug-eluting stents deployed in the left main coronary artery.

Two cases of drug-eluting stent restenosis after percutaneous coronary intervention in the left main coronary artery and its bifurcation are presented. An off-pump coronary artery bypass grafting following in-stent restenosis was performed. Drug-eluting stents have shown a reduced frequency of in-stent restenosis and a good safety profile compared with bare metal stents. However, intervention with drug-eluting stents for left main coronary artery disease should be undertaken with care. It is also important to note that preoperative anti-platelet drug administration can increase the risk of major bleeding during and after emergent surgery.     

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.     

Coronary Artery Bypass Graft Versus Drug-Eluting Stent for High-Risk Proximal Left Anterior Descending Stenosis

Determining how to treat a patient with symptomatic isolated proximal left anterior descending coronary artery disease may present a challenge. Previous randomized trials comparing percutaneous coronary intervention (PCI) with bare metal stents with minimally invasive direct coronary artery bypass surgery demonstrated significantly higher reintervention rates for stenting, with similar mortality and reinfarction rates. However, current evidence suggests that the use of drug-eluting stents may reduce the need for repeat revascularization. Also, in recent studies there were fewer periprocedural complications in patients undergoing PCI, with similar death and reinfarction rates. Moreover, the quality of life for patients who have received drug-eluting stents is similar to that of patients who have undergone minimally invasive direct coronary artery bypass surgery. Therefore, PCI with drug-eluting stents is the current treatment of choice for patients with isolated proximal left anterior descending coronary artery disease, unless they have complex lesions or repeated in-stent restenosis. In this article, the current treatment options are reviewed and outlined.     

Drug-eluting stents for ST[corrected]-elevation acute myocardial infarction: do we need randomized trials?

Since their introduction, drug-eluting stents have rapidly altered modern medicine's approach to coronary artery disease. Before the development of drug-eluting stents, standard bare-metal stents were plagued by in-stent restenosis, requiring repeat revascularization in as many as 15-20% of patients during the first 6-12 months following implantation [1]. The currently approved drug-eluting stents have dramatically reduced this complication by using a polymer-impregnated coating that elutes either paclitaxel or sirolimus to inhibit smooth muscle proliferation. The pivotal TAXUS-IV [2] and SIRIUS [3] trials compared drug-eluting stents with standard bare-metal stents and found rates of target vessel revascularization ranging from 3 to 4.1% in stable coronary artery disease patients - far lower than that had been seen previously with conventional standard bare-metal stents. After their approval in April 2003, drug-eluting stents use in clinical practice expanded rapidly. Within 9 months of their introduction, drug-eluting stents comprised 35% of all stent implantations in the United States [4]. In the last year at our own institution, drug-eluting stents comprised over 85% of all stents implanted. Despite their extensive use, data regarding the efficacy and safety of drug-eluting stents in certain clinical scenarios are limited. To date, the only published data supporting drug-eluting stents in ST[corrected]-elevation acute myocardial infarction come from the retrospective Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital registry [5] and the randomized, controlled single high-dose bolus tirofiban and sirolimus-eluting stent vs. abciximab and bare-metal stent in myocardial infarction study [6]. In this chapter, we discuss the theoretical risks and benefits of drug-eluting stents for ST elevation acute myocardial infarction, the available data regarding their use, and the areas in which future studies are needed.     

From randomized trials to routine clinical practice: an evidence-based approach for the use of drug-eluting stents

The availability of drug-eluting stents has resulted in a paradigm shift in the management of patients with coronary artery disease with a substantial increase in the percentage of patients being revascularized percutaneously rather than surgically. Since its introduction, there has been a tremendous increase in the use of drug-eluting stents with nearly 90% of patients in the US who undergo percutaneous interventions receiving drug-eluting stents. The promising results of several randomized trials that demonstrated a profound reduction in restenosis rates compared with bare-metal stents, underscores the unprecedented enthusiasm among the cardiology community to adopt this new technology swiftly. Data regarding the safety and superiority of drug-eluting stents abound, and it is imperative for the practicing clinician to review and apply them in appropriate clinical settings. In this review, we present general concepts of drug-eluting stents, and attempt to summarize the available data on the approved drug-eluting stents in a variety of patient and lesion subsets. In addition, we share some insights regarding the potential limitations, and issues specific to drug-eluting stents.     

EXCEL支架在慢性闭塞病变介入治疗中的应用及疗效观察

目的总结冠状动脉性心脏病(冠心病)慢性完全闭塞(chronic total occlusion,CTO)病变经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗中EXCEL生物降解药物涂层支架的应用及3年随访结果,评价其在CTO病变的疗效及安全性。方法2006年1月至2009年3月入住成都军区昆明总医院,冠状动脉造影确诊CTO病变并行PCI治疗患者185例,靶病变均植入EXCEL支架,常规二联抗血小板治疗至少6个月。术后6个月、1年、2年、3年临床及冠状动脉造影随访,以主要心血管事件(major adverse cardiac events,MACE)发生率、再狭窄率(in-stent restenosis,ISR)、血运重建率为研究终点,同时了解亚急性及晚期支架内血栓发生率。结果共147例CTO病变血管开通,即刻血管开通率为79.5%(147/185);共201处闭塞病变中,26处导丝无法通过,8处导丝通过闭塞病变后球囊无法跨越病变部位,靶血管开通率83.1%;闭塞时间12个月以内及超过12个月的靶血管开通率分别为87.5%、62.4%,有桥侧支存在者PCI治疗成功率低于无桥侧支者,断端呈刀切状的成功率低于鼠尾状(P0.05)。术中无死亡病例;术后6个月、1年、2年、3年冠状动脉造影复查率分别为30.8%、19.5%、15.1%、10.3%,MASE发生率分别为3.2%、2.3%、1.95、4.0%,再狭窄率分别为8.8%、8.3%、7.1%、5.3%;发生亚急性、晚期支架内血栓各1例,发生率分别为0.6%、0.1%,无急性支架内血栓事件。结论EXCEL支架应用于CTO病变PCI治疗中安全有效,没有增加MACE发生率及支架内血栓事件。     

Drug-eluting stents

Percutaneous coronary intervention has evolved dramatically over the past 25 years as coronary stents replaced stand-alone balloon angioplasty. Improvements in stents were made in the 1990s, but a breakthrough occurred in early 2000 with the development of stents that eluted pharmacology agents directly into the vessel wall by means of a controlled release from a durable polymer coating. Various drug-eluting stents were developed,each varying with its delivery platform, polymer coating (or absence of coating),and drug selected for elution. This article describes the clinically available and late developmental drug-eluting stent programs targeted for treating patients who have coronary artery disease.     

不同支架植入方式对小血管支架内再狭窄的影响

目的:观察不同支架植入方式对小血管（血管直径≤2.75 mm）支架内再狭窄的影响。方法: 对69（男51,女18）例患者共111处病变进行治疗,实验组（n=38）直接植入支架64枚（雷帕霉素药物洗脱支架53枚,紫杉醇药物洗脱支架11枚）,对照组（n=31）预扩张后植入支架47枚（雷帕霉素药物洗脱支架41枚,紫杉醇药物洗脱支架6枚）,两组患者术后即刻行冠脉血管内超声(IVUS)检测最小支架直径及横截面积。术后有胸闷胸痛症状患者即刻行冠脉造影术及IVUS,无症状患者6个月后复查。通过IVUS检测,对两组管腔丢失及支架内再狭窄率进行比较。结果: 两组支架植入术后即刻最小支架直径实验组为（2.38±0.26）mm,对照组为（2.34±0.24）mm（P＞0.05）;支架横截面积实验组为（4.5±1.0）mm2,对照组为（4.3±0.9）mm2（P＞0.05）;6个月随访后复查两组管腔丢失,实验组为（1.44±0.30）mm,对照组为（0.98±0.24）mm（P=0.01）;支架内再狭窄发生率实验组为15 %;对照组为30%（P＜0.05）。结论: 对冠状动脉小血管病变患者直接药物洗脱支架植入组支架内再狭窄发生率低于预扩张后支架植入组。     

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.     

An evidence-based approach to the use of drug-eluting stents in clinical practice

Less than a year after their release, drug-eluting stents are being used in more than 70% of patients who undergo percutaneous intervention for obstructive coronary disease in the United States. This unprecedented quick adoption was fueled by results of several randomized trials that demonstrated a profound reduction in restenosis rates compared with bare-metal stents. Subset analysis of the drug-eluting stent trials shows a strong restenosis reduction rate across a wide range of patient characteristics; however, these broad beneficial effects are based on randomized subjects who may not represent the actual population currently being treated with coronary stents. This review presents an analysis of the available data on the approved drug-eluting stents, including patient subsets that may or may not benefit; potential stent-specific complications; and a discussion of costs, risks, and cost-effectiveness.     

Drug-eluting stents versus bare metal stents in percutaneous coronary interventions (a meta-analysis)

This meta-analysis combined the results of randomized clinical trials to compare the efficacy of drug-eluting stents with that of bare metal stents in percutaneous coronary interventions to ascertain which revascularization strategy is most safe and effective. The literature identified 13 published studies, and 8 were included in the main meta-analysis, thus allowing a meta-analysis on 3,860 patients for the effect on all major adverse clinical events (MACEs) combined and for target vessel revascularization. Meta-analyses were performed for combined MACEs, patient MACEs, and thrombosis. Regression meta-analyses were performed to examine the effect of certain variables on the efficacy of drug-eluting stents compared with bare metal stents. Meta-analysis of all trials showed that drug-eluting stents produced significant decreases in the need for percutaneous revascularization (relative risk [RR] 0.30, 95% confidence interval [CI] 0.22 to 0.40) and coronary artery bypass grafting (RR 0.54, 95% CI 0.32 to 0.89). Drug-eluting stents significantly decreased all MACEs combined (RR 0.40, 95% CI 0.33 to 0.49) but were not associated with an increased risk of stent thrombosis or death. These results were confirmed at analysis as stratified by type of eluting stent, because the need for percutaneous revascularization was significantly lower for sirolimus-eluting stents (RR 0.23, 95% CI 0.15 to 0.35) and paclitaxel-eluting stents (RR 0.39, 95% CIl 0.29 to 0.53).     

Treatment of unprotected left main coronary artery disease with drug-eluting stents: is it time for a randomized trial?

The treatment of unprotected left main coronary artery disease by percutaneous intervention represents a considerable challenge for interventional cardiologists. The American College of Cardiology/American Heart Association guidelines currently recommend surgical revascularization for this disorder and percutaneous interventions have thus far been performed only in exceptional cases, albeit with positive results in some patients. Technical limitations, however, including stent restenosis, limit the application of this technique at present. The availability of drug-eluting stents, which are associated with a reduction in angiographic restenosis, might change this situation. Preliminary results show that the implantation of drug-eluting stents for unprotected left main coronary artery lesions is a feasible and safe approach. Randomized clinical trials comparing the use of drug-eluting stents with coronary artery bypass surgery for unprotected left main coronary artery disease are the next step, but can such trials be contemplated at this stage? In this review we present an overview of the findings to date and discuss the direction that research should now take.     

Intravascular ultrasound imaging in the diagnosis and treatment of spontaneous coronary dissection with drug-eluting stents

Spontaneous coronary artery dissection is a rare cause of coronary ischemia. Its prognosis is uncertain and the optimal treatment is not fully defined. We report a case of spontaneous dissection of the left anterior descending artery in a healthy post-menopausal woman, in whom the initial strategy of medical therapy was unsuccessful. After repeated angiography, we implanted 2 drug-eluting stents using intravascular ultrasound guidance with excellent immediate result and long-term symptomatic relief. This is the first report of implantation of drug-eluting stents in spontaneous coronary dissection.