Long-term results of implantation of bioengineered and drug-eluting stents in patients with coronary heart disease: comparative characteristics of predictors of poor prognosis

The purpose of the investigation was to study the morphological and clinical characteristics affecting the long-term prognosis after implantation of bioengineered and drug-eluting stents in patients with coronary heart disease (CHD). The investigation covered 2362 patients with CHD. Genous bioengineered stents were implanted in 316 patients; Cypher rapamycin-eluting stents were in 2046 patients. The independent poor factor for complications was discontinuation of antiaggregatory therapy due to surgical interventions of different types in the drug-eluting stent group and stenting of extensive stenoses in the bioengineered stent group.     

Long-term outcome after coronary stenting

The present review assesses the data on long-term outcome after coronary stenting. Histological, angiographical and intravascular imaging data have shown that the insertion of stents constitutes only a transient stimulus to lumen renarrowing, that this process is almost complete at 6 months and that a certain degree of neointima regression is also possible after this time. Clinical data have confirmed the sustained benefit of stenting in the long term. Careful selection of optimal stent designs and application of the recent advances in adjunctive pharmacological therapy are currently effective strategies to improve both short-and long-term results with coronary stenting. However, further efforts are needed and are ongoing to combat restenosis, a process that counters the excellent short-term results of stenting in the long term.     

Biodegradable stents as a platform to drug loading

Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.     

Results of coronary stenting in relation to the length of an implanted stent

The paper considers the impact of the length of an implanted stent on the early and late outcomes of intracoronary stenting. The study included 177 patients on a retrospective basis. They all underwent intracoronary stenting of 215 stenoses. All the patients were divided into three groups in relation to the length of an implanted segment (under 20 mm, 20-30 mm, and under 30 mm). In 16 (9.04%) of the 177 patients, for complete stenosis correction, several, but not one, stents were inserted, i.e. multiple stenting of a coronary stenting was performed. The stents were implanted by the conventional procedure. There was no significant difference in clinical and angiographic success rates between the patients of all three groups. There were no complications, such as transmural myocardial infarction and deaths in any groups. Acute stent thrombosis was noted only in 1 (1.8%). There was no significant difference in the incidence of subacute stent thrombosis between Groups 2 and 3 patients. No case of subacute thrombosis of implanted stents was noted in Group 1 patients. Thus, acute and subacute stent thromboses were observed in 4 (2.3%) patients, they being all from Groups 2 and 3. There was no significant difference in the development of restenosis between Groups 1 and 2 and Groups 2 and 3. At the same time, restenosis significantly more frequently developed in patients from Group 3 than in those from Group 1. Thus, the findings indicate that the length of a stented segment is an important factor that influence both early and late outcomes of intracoronary stenting.     

Methods to improve dose uniformity for radioactive stents in endovascular brachytherapy

Intravascular brachytherapy (IVBT) has rapidly gained acceptance as a new treatment modality for reducing restenosis and improving the success rate of percutaneous transluminal coronary angioplasty (PTCA). Recent clinical results on patients treated with beta-emitting 32P stents suggest that radiation reduces in-stent restenosis but may exacerbate neointimal growth at the edges of the stents. This has been referred to as the "candy wrapper effect." It is well known that radioactive stents yield extremely inhomogeneous dose distributions, with low doses delivered to tissues in between stent struts, at the ends of the stent, and also at depth. Some animal model studies suggest that low doses of radiation may stimulate rather than inhibit neointimal growth in an injured vessel, and it is hypothesized that dose inhomogeneity at the ends of a stent may contribute to the candy wrapper effect. We present here a theoretical study comparing dose distributions for beta stents vs. gamma stents; "dumbbell" radioactive loaded stents vs. uniformly loaded stents; and stents with alternate strut design. Calculations demonstrate that dose inhomogenieties between stent struts, at the ends of stents, and at depth can be reduced by better stent design and isotope selection. Prior to the introduction of radioactive stents, criteria for stent design included factors such as trackability, flexibility, strength, etc. We show here that if stent design also includes criteria for strut shape and spacing that improved dose distributions are possible, which in turn could reduce the candy wrapper effect.     

Stent thrombosis associated with first-generation drug-eluting stents: issues with antiplatelet therapy

Notice of the rare but catastrophic occurrence of stent thrombosis in association with deployment of drug-eluting stents has focused attention on the adequacy of the current dual antiplatelet regimen of aspirin and clopidogrel. Some patients will not respond to clopidogrel and a glycoprotein (GP) IIb/IIIa inhibitor may be strongly considered during stenting procedures, especially in high-risk patients or those not receiving pretreatment with clopidogrel. Insisting upon and confirming adherence to antiplatelet therapy are complicated tasks, especially because the reasons for premature discontinuation are myriad, from cost to bleeding complications to the need for minor surgery. Nevertheless, the concern about adherence to antiplatelet therapy represents a new and significant clinical reality in our stenting era, one previously less appreciated with the deployment of bare metal stents. (Neth Heart J 2007;15:148-50.)     

Effects of bifurcation-specific and conventional stents on coronary bifurcation flow. An experimental and numerical study

Our paper builds on existing research into conventional bare metal stents in order to assess new devices specifically designed for coronary bifurcation angioplasty. The first aim is to validate the numerical model against data from in vitro experiments on stented coronary phantoms. A surface mesh was built in accordance with micro-computed tomography images obtained from coronary stents implanted in silicone models and used for numerical analysis. Computational simulations for steady and unsteady cases generally agreed with their experimental counterparts. A second objective is to compare the hemodynamic performance of one of these new devices (Stentys) to that of conventional devices and stenting techniques in a simplified coronary bifurcation model. Four different coronary bifurcation stenting techniques were analyzed. We have focused on factors contributing to restenosis, such as wall shear stress (WSS), oscillatory shear index (OSI), pressure loss, and local normalized helicity (LNH). It was found that bifurcation-specific stents implanted in the side branch led to increased malapposition. This effect has proved to be more important than stent specific design characteristics such as strut size (different for conventional and Stentys stent). This conclusion is confirmed by means of drop in pressure and mechanical energy loss rate calculation; for the latter, the increase ranged from 9% to 17%, depending on the stenting technique, when dedicated stents were implanted in the side branch. The behavior patterns presented in this study should be double-checked against those obtained in more realistic geometries.     

Cardiovascular stent design and vessel stresses: a finite element analysis

Intravascular stents of various designs are currently in use to restore patency in atherosclerotic coronary arteries and it has been found that different stents have different in-stent restenosis rates. It has been hypothesized that the level of vascular injury caused to a vessel by a stent determines the level of restenosis. Computational studies may be used to investigate the mechanical behaviour of stents and to determine the biomechanical interaction between the stent and the artery in a stenting procedure. In this paper, we test the hypothesis that two different stent designs will provoke different levels of stress within an atherosclerotic artery and hence cause different levels of vascular injury. The stents analysed using the finite-element method were the S7 (Medtronic AVE) and the NIR (Boston Scientific) stent designs. An analysis of the arterial wall stresses in the stented arteries indicates that the modular S7 stent design causes lower stress to an atherosclerotic vessel with a localized stenotic lesion compared to the slotted tube NIR design. These results correlate with observed clinical restenosis rates, which have found higher restenosis rates in the NIR compared with the S7 stent design. Therefore, the testing methodology outlined here is proposed as a pre-clinical testing tool, which could be used to compare and contrast existing stent designs and to develop novel stent designs.     

Comparison of coronary artery dynamics pre- and post-stenting

Stents have dramatically improved the treatment of coronary artery disease. Since the implantation of stents changes the geometry and dynamics of the coronary artery, it is reasonable to hypothesize that some of these changes may have an important effect on the development of atherosclerosis by modulating the mechanical environment. In this paper, we presented a method to compare the geometric dynamics of the coronary artery before and after stenting using biplane angiography. Two cases are reviewed and a number of parameters are proposed to describe the longitudinal change of the vessel before and after stenting. This analysis technique has the potential to identify some aspects of stent design and procedure that might improve the success rate with this therapeutic approach.     

Clinical outcomes of long coronary stents: a single-center experience

BACKGROUND: Coronary artery stenting is particularly useful during percutaneous coronary intervention for long lesions previously associated with a low procedural success rate and a high complication rate of dissection and occlusion. Current treatment options include implantation of a single long stent, multiple contiguous stents, or 'spot' stenting. However, multiple stent implantation may result in sections of overlapping stent or gaps of unstented segments and is an independent predictor of restenosis. The early and intermediate clinical outcome of single and multiple long stent (>/= 30 mm) implantation is not established. METHODS AND RESULTS: The authors retrospectively identified 123 consecutive patients who had undergone stenting using one or more long coronary stents. Baseline clinical data, procedural outcomes and completed clinical follow-up to 52 weeks were obtained by case-note review. The majority (69%) required intervention for stable coronary disease. Seventy-seven per cent of lesions were either type B2 or C and only 2% were in saphenous vein grafts. The procedural success rate was 94%. A total of 15 major events occurred in 13 patients (11%). Ten acute events occurred and five events were during the follow-up period from 30 days to 52 weeks. Two patients died, one from uncontrolled bleeding secondary to the use of antithrombotic agents and one at four weeks due to sudden death. One patient had a postprocedural infarct. Two patients required in-hospital repeat revascularization for acute vessel closure and eight required revascularization during follow-up (three cases of occlusion/thrombosis and five cases of restenosis). CONCLUSIONS: The use of long coronary stents (>/= 30 mm) for the treatment of long diffuse native vessel disease, saphenous vein graft disease and long coronary dissections is associated with a reasonable procedural success rate and acceptable early and intermediate-term clinical outcomes.     

A new stent with streamlined cross-section can suppress monocyte cell adhesion in the flow disturbance zones of the endovascular stent

We proposed a new stent with streamlined cross-sectional wires, which is different from the clinical coronary stents with square or round cross-sections. We believe the new stent might have better hemodynamic performance than the clinical metal stents. To test the hypothesis, we designed an experimental study to compare the performance of the new stent with the clinical stents in terms of monocyte (U-937 cells) adhesion. The results showed that when compared with the clinical stents, the adhesion of U-937 cells were much less in the new stent. The results also showed that, when Reynolds number increased from 180 (the rest condition for the coronary arteries) to 360 (the strenuous exercise condition for the coronary arteries), the flow disturbance zones in the clinical stents became larger, while they became smaller with the new stent. The present experimental study therefore suggests that the optimization of the cross-sectional shape of stent wires ought to be taken into consideration in the design of endovascular stents.     

Delivery and release of nitinol stent in carotid artery and their interactions: a finite element analysis

Carotid angioplasty and stenting (CAS) has emerged as an effective alternative to carotid endarterectomy, and nitinol stents are commonly used in CAS. To evaluate biomechanical properties of nitinol carotid stents and their interactions with carotid arteries, a finite element method (FEM) model was built which is composed of a stenotic carotid tissue, a segmented-design nitinol stent and a sheath. Two different stents were considered to show the influence of stent design on the stent-vessel interactions. Results show that the superelastic stents were delivered into the stenotic vessel lumen through the sheath and self-expanded in the internal and common carotid artery. The stent with shorter struts may have better clinical results and the different stent designs can cause different carotid vessel geometry changes. This FEM can provide a convenient way to test and improve biomechanical properties of existing carotid stents and give clues for new nitinol carotid stent designs.     

Use of "Cypher" sirolimus-eluting stents in coronary heart disease patients with different types of coronary arterial lesions

The purpose of our study was to assess the immediate and late results of treatment with Cypher drug-eluting stents (Cordis, Johnson & Johnson, USA) in patients with coronary heart disease (CHD). This was a prospective study that included 738 patients who had been implanted Cypher stents in May 2002 to March 2006. The patients' mean age was 56 +/- 9 years; there were 87% of males. The patients were randomly included into the study and they underwent coronary stenting in the routine laboratory setting. A control group comprised 162 patients who had undergone Velocity or Sonic nondrug-eluting stents of the same firm, which had the similar structure. The groups did not differ in clinical characteristics. 827 stenoses in the eluting stent group and 225 stenoses in the control group were subject to revascularization. The immediate cure rate was 95 and 94%, respectively. The total number of events (myocardial infarction, emergency coronary bypass surgery, subacute occlusion of a stented segment) was 2.3% in the eluting stent group and 2.4% in the control group. A repeated examination 1 year after surgery was made in 482 and 119 patients in the drug-eluting and nondrug-eluting groups, respectively. During the follow-up, one patient died of a extracardiac cause and 3 (0.6%) patients underwent coronary bypass surgery in the nondrug-eluting stent group; there were no deaths and 2 (1.6%) patients had coronary bypass surgery in the control group. In the eluting stent group, there were fewer cases of repeated endovascular procedures of target stenosis revascularization than in the control group (3.7% versus 11.7%; p < 0.0005). In the eluting stent group, the total number of unfavorable cardiovascular events was significantly less than that in the control group and it amounted to 3.3% as compared with 15.9% in the non-eluting stent group; p < 0.0005. Cardiovascular event-free survival was significantly higher in the eluting stent group: 92% versus 77% in the non-eluting stent group (p < 0.0005).     

The role of acute wall recoil and late restenosis: results of the OCBAS trial (Optimal Coronary Balloon Angioplasty with Provisional Stenting versus Primary Stent)

Early deterioration of minimal luminal diameter immediately after PTCA, has been associated with an increase of late restenosis. Lesions with no early loss after PTCA have a low restenosis rate. Coronary stents reduce restenosis in lesions exhibiting early wall recoil. The purpose of the OCBAS study was to compare two strategies during coronary interventions; provision vs. elective stenting. 116 patients with good PTCA results were randomized to stent (n = 57) or to optimal PTCA (n = 59). After randomization in PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting). Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study; 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; P < 0.03). However, late loss was significantly higher in the stent than the PTCA groups (0.63 +/- 0.59 vs. 0.26 +/- 0.44, respectively; P = 0.01). Hence, net gain with both techniques was similar (1.32 +/- 0.3 vs. 1.24 +/- 0.29 mm for the stent and PTCA groups respectively; P = NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; P = NS) and TVR (17.5 in stent vs. 13.5% in PTCA; P = NS) were also similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (P = NS). Overall costs (hospital and follow-up) were US$591,740 in the stent versus US$398,480 in the PTCA group (P < 0.02). The strategy of the PTCA with delay angiogram and provisional stent if early loss occurs, had similar restenosis rate and TVR than universal use of bare stents.     

冠状动脉内重叠支架置入术的临床研究进展

重叠支架置入术是临床上用来治疗冠状动脉弥漫性长病变的常用方法,以往曾采取重叠裸金属支架置入术,但其临床预后不佳,目前较为常用的重叠药物洗脱支架置入术被认为相对安全、有效,但仍存在许多潜在问题。本文介绍了适合使用重叠支架置入术进行治疗的冠状动脉病变的特点,回顾了重叠裸金属支架的临床应用情况,阐述了近年来药物洗脱支架的发展以及重叠药物洗脱支架置入术的优势,比较了四种负载不同药物的药物洗脱支架同种重叠置入后的临床疗效,观察了异种药物洗脱支架混合重叠置入后的临床特点和支架重叠段对临床预后的影响,分析了重叠支架置入术与几种其它治疗冠状动脉弥漫性长病变方法的应用区别,并对新一代药物支架的重叠应用进行了展望。     

Immediate and long-term outcomes of coronary stenting in relation to stent implantation pressure in patients with coronary heart disease

The paper evaluates the pressure impact of implantation of intracoronary stents of different designs on the immediate and long-term outcomes of stenting. A retrospective study included 192 patients. Matrix and wire stents were implanted in 97 (50.5%) and 95 (49.5%) patients, respectively. In one part of the patients, the coronary stent was implanted under nominal pressure, in the other, the stent after implantation was extended with a balloon by using high pressure. Good immediate angiographic and clinical results were obtained in all 192 patients. Thirty three (17.2%) patients were found to have coronary spasm at the site of a stent. There was no significant difference in the development of coronary spasm, which was associated with the type of an implanted (matrix or wire) stent and with the pattern of its implantation (under high or nominal pressure). Dissection along the stent edges developed in 17 of the 192 patients, which amounted to 8.8%. It significantly more frequently developed in patients from Subgroup IA than in those from Subgroup IB. There was no significant difference in the development of restenosis in patients after implantation of matrix or wire stents and in the relation to the stent implantation pressure.     

Provisional stenting in small vessels

Based on the currently available data, the strategy of routine stent placement in unselected lesions located in small coronary arteries provides good immediate results but is still associated with a high incidence of in-stent restenosis. Randomized trials comparing elective stenting with balloon angioplasty have not provided the demonstration that routine stenting is the best strategy for percutaneous intervention in coronary arteries with a reference diameter smaller than 2.75-3.0 mm. This paper describes the rationale for provisional stenting in this clinical setting and reviews the role of quantitative coronary angiography, intracoronary ultrasound and intracoronary Doppler measurements in the identification of lesions that would benefit from adjunctive stent placement after balloon angioplasty and in guiding stent implantation.     

Drug-eluting stents: from bench to bed

The introduction of stents to clinical practice in 1987 was the major breakthrough in the field of percutaneous coronary intervention (PCI). The use of stenting has drastically improved the outcomes of traditional PCI. First stents were approved for bailout and treatment of dissections, reducing dramatically the need for emergent coronary artery bypass grafting (CABG) as a result of vessel closure during PCI. Later stents were proven to reduce the restenosis rate of PCI from 30%-40% with balloon angioplasty to 15%-20% with stents, primarily by eliminating elastic recoil and vascular remodeling as shown by intravascular ultrasound (IVUS) studies. These outcomes have led to a wide acceptance of stenting as the strategy of choice for more than 80% of all PCI procedures performed. The current review focuses on the following topics: (1) strategies in drug selection to reduce neointimal proliferation, (2) stent designs and polymer selection as a platform for drug-eluting stents, (3) review of major preclinical and clinical experimental work performed in the field, and (4) a discussion of the potential and limitations of the technology.     

Contribution of recipient-derived cells in allograft neointima formation and the response to stent implantation

Allograft coronary disease is the dominant cause of increased risk of death after cardiac transplantation. While the percutaneous insertion of stents is the most efficacious revascularization strategy for allograft coronary disease there is a high incidence of stent renarrowing. We developed a novel rabbit model of sex-mismatched allograft vascular disease as well as the response to stent implantation. In situ hybridization for the Y-chromosome was employed to detect male cells in the neointima of stented allograft, and the population of recipient derived neointimal cells was measured by quantitative polymerase chain reaction and characterized by immunohistochemistry. To demonstrate the participation of circulatory derived cells in stent neointima formation we infused ex vivo labeled peripheral blood mononuclear cells into native rabbit carotid arteries immediately after stenting. Fourteen days after stenting the neointima area was 58% greater in the stented vs. non-stented allograft segments (p = 0.02). Male cells were detected in the neointima of stented female-to-male allografts. Recipient-derived cells constituted 72.1+/-5.7% and 81.5+/-4.2% of neointimal cell population in the non-stented and stented segments, respectively and the corresponding proliferation rates were only 2.7+/-0.5% and 2.3+/-0.2%. Some of the recipient-derived neointimal cells were of endothelial lineage. The ex vivo tagged cells constituted 9.0+/-0.4% of the cells per high power field in the stent neointima 14 days after stenting. These experiments provide important quantitative data regarding the degree to which host-derived blood-borne cells contribute to neointima formation in allograft vasculopathy and the early response to stent implantation.     

Long-term clinical efficiency of endovascular treatment using Cypher rapamycin-eluting stents in patients with coronary heart disease

The study was undertaken to analyze the long-term results in patients with coronary heart disease (CHD) one year or more after Cypher stent implantation. It covered 1221 patients. One-, two-, and three- vessel lesions were observed in 693 (56.8%), 344 (28.2%), and 184 (15%) patients, respectively. A total of 1967 Cypher stents were implanted. The results of treatment were analyzed 1 and 2 years after intervention. The efficiency of a procedure was evaluated by the following parameters: the presence or absence of anginal symptoms, the presence and absence of complications (fatal outcome, myocardial infarction). The following morphological parameters: the rate of restenosis and that of late stent thrombosis were also assessed. The results of one- and two-year follow-ups were used to make a multivariate analysis of the clinical and morphological predictors of coronary complications (fatal outcome, myocardial infarction, recurrent angina pectoris) in the late period, as well as the predictors of restenosis and late stent thrombosis. Restenosis following 1 year of Cypher stent implantation is 3.1%. The factors that significantly increase the risk of this complication within the first year are diabetes mellitus and revascularization in the patients operated on. The one-year rate of Cypher stent thromboses is 1.6%. Patients' discontinuation of antiaggregant therapy is the sole factor that significantly increases the rate of their late thromboses in this period. Within the second year of a follow-up, the rate of late Cypher stent thromboses is 1.8%. The risk of this complication is significantly increased by factors, such as a lengthy (more than 3 mm) stented portion, renal failure, and less than 40% left ventricular ejection fraction.