Drug-eluting stents: a multidisciplinary success story

Coronary stenting is the most common form of interventional treatment for symptomatic coronary artery disease. In-stent restenosis following bare metal stent (BMS) placement is the most common cause of procedural failure and occurs as a result of vessel wall trauma secondary to balloon angioplasty and stent deployment that results in an overly aggressive healing response (neointimal hyperplasia) that overgrows the stent lumen and causes vascular narrowing. Drug-eluting stents (DES) are specialized vascular stents capable of delivering drugs to the arterial wall in a controlled manner such that neointimal hyperplasia is reduced or prevented, luminal patency is preserved, coronary blood flow is maintained and the patient is spared a repeat procedure to re-open the vessel. The objectives of the review are to provide an overview of the major contributions that a broad range of disciplines have made to the design and development of drug-eluting stents and to summarize future directions of these fields of research. Engineers and biomaterials scientists have explored relationships between stent design and stent performance and work continues to optimize stent design and biocompatibility of stent biomaterials. Pharmaceutical scientists are continually expanding the range of candidate drugs for pharmacological intervention, and improving the technology using novel coatings to modulate drug release. Clinical scientists are investigating issues such as long-term safety and efficacy, new applications of drug-eluting stents and optimal deployment techniques.     

Perspectives of Drug-Eluting Stents

Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD). Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation. Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures. Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis. Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation. When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models. Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries. Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation. Results are also very encouraging with paclitaxel-coated stents. However, it needs to be proven that current drug-eluting stents will produce similar results in ‘real life’ interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx Velocity? balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns. With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic and improved molecules), we think that in the next few years the practice of interventional cardiology may undergo major changes. A new era of dramatic improvements in the treatment of CAD may have dawned. The prospect of approval of this technology should herald a host of clinical trials to revisit basic assumptions about the place of coronary stenting in the contemporary care of obstructive (and nonobstructive) CAD.     

Can Angiotensin Receptor Antagonists Prevent Restenosis After Stent Placement?

Restenosis rates after coronary stent implantation in complex lesions are between 30 and 50%. Neointimal hyperplasia promoted by complex interaction between cellular and acellular elements, such as cytokines and growth factors, is thought to be the primary process responsible for restenosis. The risk of in-stent restenosis is increased in patients with a history of restenosis after percutaneous transluminal coronary angioplasty, in long lesions, in total occlusions, in patients with diabetes mellitus, in small vessels, in the proximal parts of the left anterior descending coronary artery and in cases of stent oversizing. In-stent restenosis represents a serious economic burden on society because treatment strategies include expensive approaches such as cutting-balloon angioplasty, rotational atherectomy and brachytherapy. A number of pharmacological agents, including ACE inhibitors, have been unsuccessful in preventing restenosis. Alternative procedures such as brachytherapy, radioactive stents and drug-eluting stents are under evaluation. Although sirolimus- or paclitaxel-eluting stents have been associated with very low restenosis rates over durations of 6 to 12 months, the long-term efficacy and tolerability of this approach is currently being investigated. Although ACE inhibitors have failed in reducing restenosis rates, the selective angiotensin II type 1 (AT₁) receptor antagonist valsartan has shown encouraging results in the single-center Valsartan for Prevention of Restenosis after Stenting of Type B2/C lesions trial (ValPREST). The ValPREST trial is the first randomized, placebo-controlled study to have evaluated the effect of an angiotensin receptor antagonist on in-stent restenosis in a moderate number of patients. Compared with ACE inhibitors, angiotensin receptor blockers exert additional effects on the pathophysiological processes which lead to restenosis. Angiotensin receptor antagonists may affect several mechanisms involved in neointimal hyperplasia such as decreasing circulating cytokine and growth factor levels and reducing neutrophil activation, especially after stenting in acute coronary syndromes, but the results need to be confirmed in a large multicenter trial. The question whether long-term therapy, with an oral angiotensin receptor antagonist, is cost-effective and whether angiotensin receptor antagonists should be used as an add-on therapy to drug-eluting stents, requires clarification.     

Paclitaxel-eluting stents in coronary artery disease.

PURPOSE: Clinical information regarding paclitaxel-eluting coronary artery stents is reviewed. SUMMARY: Restenosis is a significant complication of percutaneous coronary intervention. Coronary artery stenting has reduced restenosis compared with traditional balloon angioplasty, although restenosis still occurs with bare-metal coronary artery stents. The pathogenesis of in-stent restenosis is believed to involve smooth-muscle-cell proliferation and migration in response to vessel injury. A neointimal layer of extracellular matrix and collagen forms, which may impinge on the vessel lumen. Paclitaxel inhibits vascular smooth-muscle-cell proliferation and reduces neointimal mass. Local delivery of paclitaxel through a coronary stent has been shown to reduce restenosis rates and percent diameter stenosis and to produce other angiographic benefits compared with bare-metal stents. Fewer major adverse coronary events are seen with paclitaxel-eluting stents, predominantly because of a reduction in the need for target-vessel revascularization with minimal impact on rates of mortality and myocardial infarction (MI). The Taxus Express(2) stent, the only approved paclitaxel-eluting stent in the United States, costs about three times as much as a bare-metal stent. Cost-effectiveness analyses are needed to determine if the Taxus stent is cost-effective in clinical practice. CONCLUSION: Paclitaxel-eluting stents reduce the rates of restenosis and target-vessel revascularization compared with bare-metal stents and have comparable effects on mortality and MI rates.     

Drug-eluting stents in peripheral vascular disease: eliminating restenosis

Transcatheter endovascular therapy for peripheral atherosclerotic disease has become more popular. In general, good results have been reported in focal aortoiliac disease. However, the long-term patency of angioplasty in longer, more distal lesions has been less satisfactory. Stenting has not been shown to improve long-term patency compared to angioplasty alone. Drug-eluting stents have shown promise in preventing coronary restenosis, and preliminary results in peripheral arterial disease are encouraging. This review article will discuss the current status of endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease, the theoretic and experimental basis for the use of drug-eluting stents, and the preliminary results in human studies.     

Antegrade iliac artery stent implantation for the temporal and spatial examination of stent-induced neointimal hyperplasia and alterations in regional fluid dynamics

INTRODUCTION: Neointimal hyperplasia remains an important problem after stent implantation. Previous investigations examining vascular responses to stent implantation and effects of drugs have used a retrograde deployment approach that may inadvertently alter the local fluid dynamics surrounding the stent. We present a model of antegrade iliac artery stent implantation that facilitates the analysis of stent-induced alterations in neointimal hyperplasia and wall shear stress in vivo. METHODS: Stent delivery catheters were inserted through the left carotid artery in anesthetized rabbits (n=37). Catheters were advanced under fluoroscopic guidance to the distal iliac arteries, where the stent was deployed. Hemotoxylin and eosin (H&E) staining of unstented and stented vascular sections was performed 21 days after implantation. RESULTS: Selective unilateral stent implantation was successful in 32 of 37 rabbits. No histological abnormalities were observed in the aorta, contralateral unstented iliac, or distal femoral arteries. Neointimal hyperplasia was localized to the stented region. DISCUSSION: The model of stent implantation was relatively easy to perform and produced selective neointimal hyperplasia within the stented region without evidence of damage, cellular proliferation, or flow disruption in the surrounding normal arterial vessels. The model will allow detailed examination of the influence of stent implantation on indices of wall shear stress, neointimal hyperplasia, the mechanisms of cellular proliferation in vivo, and their modification by drugs.     

Eluvia™ peripheral stent system for the treatment of peripheral lesions above the knee

ABSTRACT

Introduction: Drug-eluting stents promise to reduce restenosis following endovascular treatment of diseased arteries, but technologies used in peripheral arteries of the leg have not yet achieved desired success rates.

Areas covered: The rationale behind the development of the Eluvia^TM Drug-Eluting Vascular Stent (Boston Scientific, Marlborough, MA) is described and current preclinical and clinical evidence related to use of the stent is reviewed.

Expert opinion: Stents remain an important endovascular treatment option for femoropopliteal lesions, especially those that are long, occluded, and calcified. Drug-eluting stent technologies show promise to improve patency rates, potentially shifting the primary treatment preference away from balloon-based treatment. The available preclinical and clinical data on treatment with Eluvia^TM suggest that prolonged paclitaxel elution in the femoropopliteal arteries prevents restenosis and may reduce the need for reintervention.     

Restenosis following implantation of bare metal coronary stents: pathophysiology and pathways involved in the vascular response to injury

This review summarizes the restenotic process that occurs after the implantation of bare metal coronary stents. The pathology of in-stent restenosis is distinct from that seen after balloon angioplasty and is characterized by neointimal proliferation and extracellular matrix deposition. The degree of neointimal proliferation is proportional to the amount of injury, the intensity of the inflammatory infiltrate and the association of stent struts with lipid-filled plaque. In-stent restenosis also appears to be associated with systemic markers of inflammation. Shear stress has an important influence on restenosis as does the presence and adhesiveness of vascular progenitor cells. Clinical predictors (e.g., artery size, stent length, diabetes, and gender) may affect the incidence of restenosis seen after stent placement. A number of catheter-based interventions have been used to treat in-stent restenosis. Although preliminary data suggest that the use of drug-eluting stents may be effective, only intracoronary radiation has shown consistent efficacy in randomized trials.     

Eluting combination drugs from stents

Cardiovascular diseases (CVD) are one of the leading causes of death across the globe. Pathogenesis of coronary artery disease (CAD) is lead by the progression of atherosclerotic lacerations in coronary arteries. Percutaneous coronary intervention (PCI) using balloon angioplasty was introduced in 1979 and was majorly used in the treatment of these lesions. Introduction of bare metal stents (BMS) has revolutionized stenting procedures overcoming elastic recoil and reducing restenosis commonly associated with balloon angioplasty, but follow up studies have shown 20–30% prevalence of in-stent restenosis (ISR), this led to the development of drug eluting stents (DES). But long-term follow up studies have shown increased liability of stent thrombosis. Boosting the development of safer and effective DES expounding for therapies like biodegradable polymer based DES, polymer free DES, bioresorbable DES and combination DES to collectively reduce neointimal hyperplasia and promote endothelial healing. In dual-DES development, a combination employing an anti-restenotic agent (for preventing VSMC's proliferation), which is released for the first few weeks, and then the second drug a pro-healing agent (promoting re-endothelialization) released after a month would be ideal. Growing understanding in the areas of polymer therapeutics, nanoscale surface modifications and gene therapy would assist in the delivery of multiple drugs, which would further help in the design of promising therapeutic strategies for the treatment of CAD using stent based therapies.     

Local vascular toxicokinetics of stent-based drug delivery

One of the major limitations of balloon angioplasty is early restenosis as a result of elastic recoil leading to vessel occlusion. The constrictive (negative) remodeling of the blood vessel is overcome by implanting a balloon expandible metal stent to dilate the artery and thereby prevent elastic recoil. However, bare metal stent implants cause mechanical injury to the intima and release of inflammatory mediators which then initiates formation of neointimal layer leading to restenosis. In-stent restenosis is histologically distinct from restenosis following balloon angioplasty, in which in-stent restenosis is accompanied by increased smooth muscle proliferation, migration, extracellular matrix and collagen synthesis leading to neointimal hyperplasia. To overcome neointimal hyperplasia, stents have been coated with pharmacological agents that inhibit smooth muscle cell proliferation and migration. The drug and polymer combination coated onto stent device is an efficient form of drug delivery system which can provide high concentrations of drug in the tissues over an extended period of time to achieve antiproliferative therapeutic effect. The permanent stent implants pose the risk of a continuous interaction between the non-biodegradable polymer coating and intimal surface leading to physical irritation, endothelial dysfunction, hypersensitivity reactions, delayed healing and excess risk of late stent thrombosis. This review highlights the relationship between local drug delivery using the stent platform, release kinetics and local vascular toxicity.     

Novel approaches for the prevention of restenosis

Restenosis, the re-narrowing of the lumen of the coronary artery, in the months following a successful percutaneous balloon angioplasty or stenting, remains the main limitation to percutaneous coronary revascularisation. Serial intravascular ultrasound studies have shown that restenosis after conventional balloon angioplasty represents a complex interplay between elastic recoil, smooth muscle proliferation and vascular remodelling, while restenosis after stent deployment is due almost entirely to smooth muscle hyperplasia and matrix proliferation. Despite intensive investigation in animal models and in clinical trials, most pharmacological agents have been found to be ineffective in preventing restenosis after percutaneous balloon angioplasty or stenting. Although studies frequently report success in the suppression of neointimal proliferation in animal models of balloon vascular injury, few of them have been successful in clinical trials. Lately, the advent of endovascular radiation, new antiproliferative agents, recombinant DNA, growth factor regulators and novel local drug delivery systems have shown promising results. In the past five years, intracoronary radiation with gamma- and beta-emitting sources has been evaluated intensively with very encouraging results. This is the first potent non-pharmacological approach that has been successful in a large number of patients in controlling excessive tissue proliferation. It is very likely that a combination of stents and pharmacological and/or non-pharmacological inhibition of neointimal hyperplasia will likely result in further reductions in the incidence if restenosis. The continued attractiveness of percutaneous coronary revascularisation, as an alternative to medical treatment or bypass surgery for patients with coronary artery disease, will depend upon our ability to control the restenotic process. Due to the vast literature on the subject, this review will focus mainly on clinical trials that show the most promise and will highlight those that warrant further investigation.     

Clinical studies with paclitaxel - eluting stent systems

Coronary artery stents mechanically buttress the arterial wall and prevent negative remodeling, leading to increased lumen gain and less angiographic and clinical restenosis as compared with balloon angioplasty alone. Although stents prevent negative remodeling, they do not eliminate restenosis, as they cause complex arterial injury triggering responses that culminate in the induction of neointimal hyperplasia. For many years after the development of balloon angioplasty and stenting, many unsuccessful attempts were made to find methods to prevent neointimal hyperplasia. In 1995, Sollot and colleagues were first to recognize the ability of the antineoplastic compound paclitaxel to limit neointimal hyperplasia formation. In 1997, Axel and colleagues were the first to demonstrate that paclitaxel locally delivered locally to the arterial wall limited neointimal hyperplasia in an animal model. After success in preclinical and human trials, the FDA approved the use of paclitaxel-eluting coronary stents in 2004 on the strength of the pivotal TAXUS trials, which demonstrated that stents utilizing a polymer coating as a paclitaxel delivery vector were effective in the prevention of restenosis. Subsequent trials have confirmed the effectiveness of paclitaxel in restenosis prevention. In these trials, paclitaxel was delivered using both polymer-coated stents and stents directly impregnated with drug, and on different stent platforms by different manufacturers. Paclitaxel eluting stents have been shown to be effective in a variety of cardiovascular lesion and patient subsets in randomized trial and registry data sets. Although there are concerns that locally delivered paclitaxel and/or its polymer delivery vehicle may lead to impaired vascular healing that may predispose to the development of stent thrombosis, pooled data analyses have confirmed an acceptable safety profile for paclitaxel-eluting coronary stents. The current generation of paclitaxel eluting stents have different performance profiles shen compared to first generation and second generation coronary stents eluting sirolimus or related compounds, especially in regard to target lesion revascularization rates. However, whether these difference translates into clinically relevant benefits remains debatable. In addition, newer paclitaxel elution techniques and newer paclitaxel-eluting stent architecture may improve the performance of paclitaxel-eluting stents. As the only approved non-limus based antiproliferative agent currently available, paclitaxel is uniquely positioned in the future of interventional vascular medicine.     

Sirolimus eluting stent: a new era in interventional cardiology?

Coronary artery stents have emerged as the preferred tool for percutaneous coronary interventions during the past decade by eliminating abrupt vessel closure and reducing restenosis compared with balloon angioplasty. While coronary artery stents prevent constrictive arterial remodeling and elastic recoil, the implantation is associated with more severe arterial vascular injury than balloon angioplasty alone. The arterial injury initiates a vasculoproliferative response with smooth muscle cell proliferation and migration as well as extracellular matrix formation, which may lead to severe neointimal hyperplasia with in-stent restenosis in 10-30% of cases. Sirolimus, a naturally occurring macrocyclic lactone, has been identified as a pharmacological cell cycle inhibitor with potent antiproliferative and antimigratory effects on vascular smooth muscle cells in vitro. The systemic administration of sirolimus has been shown to effectively reduce neointimal hyperplasia in experimental restenosis models. Subsequently, sirolimus has been incorporated at therapeutically important doses into biocompatible polymers, which made it suitable for stent-based drug elution. Investigation of sirolimus eluting stents in both experimental and clinical restenosis studies have demonstrated dramatic reductions in neointimal hyperplasia. Accordingly, sirolimus eluting stents offer an attractive mode of local drug delivery by minimizing systemic toxicity and maximizing local dose requirements. In addition, sirolimus eluting stents hold great promise to effectively prevent restenosis.     

通心络对兔外周血管球囊损伤后血栓形成及内膜增生的影响

目的观察中成药通心络对兔腹主动脉及骼动脉球囊损伤后血栓形成及内膜增生的影响。方法新西兰兔36只,随机分为3组通心络组16只,阿司匹林组11只,安慰剂组9只。各组服药剂量通心络0.38g     

Stent-based release of a selective PDGF-receptor blocker from the bis-indolylmethanon class inhibits restenosis in the rabbit animal model

Long-term success of modern therapies for myocardial ischemia is limited by restenosis, with proliferation and migration of vascular smooth muscle cells (VSMC) as key events. Since findings in recent years indicate, that the Platelet Derived Growth Factor (PDGF) is an important selective factor in mitogenic and motogenic pathways of VSMC, different concepts for reducing restenosis by inhibiting PDGF signaling have been investigated, with local delivery of small receptor kinase inhibitors looking most promising. We tested the stent-based delivery of the PDGF-receptor inhibitor D-65495, a bis(1H-2-indolyl)methanone, in the rabbit iliac artery model of restenosis. New Zealand white rabbits underwent balloon dilation of iliac arteries for implantation of D-65495-coated or non-coated (solvent, either DMSO or 90%THF / 10% DMSO) coronary stents. After 4 weeks stents were removed and neointima formation in medial and proximal/ distal stent sections was histomorphometrically and immunohistochemically analyzed.Arteries with D-65495 eluting stents showed an up to 50% reduced restenosis compared to control stents. Also, the neointimal area was reduced, but there were no significant differences in injury score. Importantly, endothelialization was similar for control stents as well as for D-65495-coated stents, suggesting absence of a general cytostatic effect of the inhibitor. The impact of D-65495 on PDGF-receptor signaling in the vessel wall was indirectly assessed by immunohistochemical staining for activated protein kinase Akt, and PCNA as a proliferation marker and revealed some reduction for the inhibitor-treated vessels. In conclusion, the application of D-65495 caused a significant decrease in neointima formation, further supporting the concept of using locally released PDGF-receptor kinase inhibitors as anti-restenotic agents.     

Sirolimus- or paclitaxel-eluting stents to prevent coronary artery restenosis

The restenosis rate is lower with stent implantation than with balloon angioplasty. Nevertheless, even with the use of stenting, restenosis still occurs in approximately one-third of patients with diabetes, small coronary vessels, and long lesions. The two drugs commonly used in eluting stents are sirolimus and paclitaxel. Systemically administered sirolimus decreased vascular proliferation in animal models. After preliminary trials showing benefit with sirolimus-eluting stents in de novo coronary lesions, the large-scale SIRIUS (Sirolomus-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial was undertaken. SIRIUS showed that sirolimus reduced restenosis and target vessel revascularisation, compared to bare stents. These benefits were also apparent in the diabetic, and small- and long vessel subgroups. The RESEARCH (Rapamycin-eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry have established that sirolimus-eluting stents are superior to bare stents in practice. Thus, the benefits of sirolimus-eluting stents over bare stents have been clearly established, and sirolimus can be considered the benchmark eluting agent for the prevention of coronary artery restenosis. Animal studies with paclitaxel-eluting stents, mainly in endothelium denuded normal vessels, have shown that paclitaxel reduces restenosis in the short-term, and that this may be a delay, rather than a prevention of restenosis. In clinical trials, stents eluting the paclitaxel derivative 7-hexanolytaxol, or paclitaxel without a polymer, delay rather than prevent restenosis. Slowing the release of paclitaxel with a polymer base in the TAXUS (Taxol(trade mark) [paclitaxel]-eluting stent) series of clinical trials reduced the revascularisation rate at 12 and 18 months, indicating that polymer-based paclitaxel is effective for longer. The results of the REALITY trial comparing the sirolimus- and paclitaxel-eluting stents in diabetics and other high-risk patients are eagerly awaited.     

Sirolimus- or paclitaxel-eluting stents to prevent coronary artery restenosis

The restenosis rate is lower with stent implantation than with balloon angioplasty. Nevertheless, even with the use of stenting, restenosis still occurs in approximately one-third of patients with diabetes, small coronary vessels, and long lesions. The two drugs commonly used in eluting stents are sirolimus and paclitaxel. Systemically administered sirolimus decreased vascular proliferation in animal models. After preliminary trials showing benefit with sirolimus-eluting stents in de novo coronary lesions, the large-scale SIRIUS (Sirolomus-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial was undertaken. SIRIUS showed that sirolimus reduced restenosis and target vessel revascularisation, compared to bare stents. These benefits were also apparent in the diabetic, and small- and long vessel subgroups. The RESEARCH (Rapamycin-eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry have established that sirolimus-eluting stents are superior to bare stents in practice. Thus, the benefits of sirolimus-eluting stents over bare stents have been clearly established, and sirolimus can be considered the benchmark eluting agent for the prevention of coronary artery restenosis. Animal studies with paclitaxel-eluting stents, mainly in endothelium denuded normal vessels, have shown that paclitaxel reduces restenosis in the short-term, and that this may be a delay, rather than a prevention of restenosis. In clinical trials, stents eluting the paclitaxel derivative 7-hexanolytaxol, or paclitaxel without a polymer, delay rather than prevent restenosis. Slowing the release of paclitaxel with a polymer base in the TAXUS (Taxol^? [paclitaxel]-eluting stent) series of clinical trials reduced the revascularisation rate at 12 and 18 months, indicating that polymer-based paclitaxel is effective for longer. The results of the REALITY trial comparing the sirolimus- and paclitaxel-eluting stents in diabetics and other high-risk patients are eagerly awaited.     

人工血管搭桥术治疗下肢动脉缺血的临床分析

目的提高人工血管搭桥术治疗下肢严重动脉缺血的临床效果。方法对1995-01～2001-06我科采用人工血管搭桥术治疗下肢严重动脉缺血24例进行分析,通过动脉造影显示闭塞分别位于近肾腹主动脉-双髂动脉、腹主动脉-双髂动脉、髂动脉、股动脉或股-动脉。结果经术后平均31个月的随访,截肢率为16.6%,阻塞率为25.0%,通畅率为58.3%.结论下肢动脉闭塞时,采用人工血管搭桥术是重建患肢血液循环通畅的有效方法,动脉造影是正确选择重建手术方式的保证。     

Sirolimus-eluting coronary stent.

PURPOSE: The mechanism of action and pharmacokinetics of sirolimus when used as part of a drug-eluting stent (DES) and the efficacy and cost of using DESs versus bare-metal stents are discussed. SUMMARY: The use of balloon angioplasty with or without coronary artery stenting is limited by the phenomenon of in-stent restenosis (ISR). Until very recently, most efforts to overcome ISR had been ineffective. The search to prevent or reduce the frequency of ISR has led to the recent development of novel coronary artery stents designed to deliver a drug that acts locally. The first DES was approved by FDA in April 2003. This stent releases sirolimus, an agent that inhibits vascular smooth-muscle-cell proliferation. To date, four major clinical trials have demonstrated the sirolimus-eluting stent to be safe and effective in preventing restenosis in de novo coronary artery lesions. CONCLUSION: The sirolimus-eluting coronary stent is associated with less ISR than non-drug-containing stents, but further investigation is needed to determine its exact place in the treatment of coronary artery occlusion.     

Renin-angiotensin system intervention to prevent in-stent restenosis: an unclosed chapter

The occurrence of in-stent restenosis is a major drawback of percutaneous transluminal coronary angioplasty with stent placement. Target vessel revascularization is necessary in 15% of patients who receive a stent. Recent advances in the development of drug-eluting stents have reduced these numbers tremendously. However refinement of antirestenotic therapies remains obligatory. The emerging interest in more physiological antirestenotic therapies might unchain an interest in the well-known inhibitors of the rennin-angiotensin system (RAS), the angiotensin-converting enzyme inhibitors, and the angiotensin II type I receptor blockers. Contradictory results overshadow the discussion of whether intervention in the RAS could prevent in-stent restenosis. This review discusses the pathophysiology of in-stent restenosis, the role of the RAS in in-stent restenosis, and the possible role of RAS intervention in the prevention of in-stent restenosis.