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.     

Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials.

OBJECTIVES: We sought to synthesize the available evidence on the effectiveness of drug-eluting stents for bare-metal in-stent restenosis. BACKGROUND: Although there is clinical evidence that drug-eluting stents are associated with better results than other treatments for in-stent restenosis, they are not yet approved for this indication. Meta-analysis of randomized trials may yield more precise estimates of treatment effects and enable a rapid adoption of effective treatments in clinical practice. METHODS: Data sources included PubMed and conference proceedings. Prespecified criteria were met by 4 randomized studies comparing sirolimus- or paclitaxel-eluting stents versus balloon angioplasty or vascular brachytherapy in 1,230 patients with bare-metal in-stent restenosis. Studies reported the clinical outcomes of efficacy and safety during a minimum of 9 months. The primary outcome was target lesion revascularization. RESULTS: No significant heterogeneity was found across trials, thus showing a similar effect size regardless of the use of balloon angioplasty or vascular brachytherapy as comparators. The risk of target lesion revascularization (odds ratio 0.35, 95% confidence interval [CI] 0.25 to 0.49; p < 0.001) and that of angiographic restenosis (odds ratio 0.36, 95% CI 0.27 to 0.49; p = 0.001) were markedly lower in patients treated with drug-eluting stents. There were no differences between patients treated with drug-eluting stents and those treated with other techniques with respect to the composite of death or myocardial infarction (odds ratio 1.04, 95% CI 0.54 to 2.03; p = 0.55). CONCLUSIONS: Drug-eluting stents are markedly superior to conventional techniques (balloon angioplasty and vascular brachytherapy) and should be considered as first-line treatment for patients with bare-metal in-stent restenosis.     

Bare-metal stent outcomes in an unselected patient population

BACKGROUND: Randomized trials have shown that drug-eluting stents (DES) substantially reduce in-stent restenosis compared with bare-metal stents (BMS). HYPOTHESIS: Revascularization event rates related to BMS restenosis may be higher in the trials setting than in real-world experience, calling into question the extent of benefit possible with widespread DES use in regular practice. METHODS: Between December 1998 and March 2003, 17,102 patients with BMS registered in the Goodroe Healthcare Solutions Data Warehouse met the inclusion criteria for this retrospective study of catheterization laboratory data. We examined the database for evidence of diagnostic angiography or percutaneous coronary intervention (PCI) readmission within 1 year after stenting. RESULTS: Repeat PCI was documented for 2070 patients, and 232 were referred for coronary artery bypass graft surgery (CABG)-in sum, 13.5% of the cohort. Stented region revascularization was observed in 8.4%: 1350 patients underwent subsequent PCI, and 84 of the patients referred for CABG had in-stent lesion recurrence. Only 1207 (7.1%) patients required stent-related PCI after 30 days, the time frame consistent with restenosis. CONCLUSIONS: In this "real-world" series, reintervention of a stented region after the first follow-up month was documented in fewer than 8% of patients in a large cohort that had received BMS. The rate of clinical events potentially related to BMS in-stent restenosis in this large, unselected patient population is substantially lower than that in the control arms of some DES trials. The incremental benefit of widespread conversion from BMS to DES may be smaller in some patient populations than is suggested by the results of those trials.     

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-Coated Balloons for Coronary and Peripheral Interventional Procedures

Paclitaxel-coated balloon (PCB) angioplasty reduces neointimal proliferation, restenosis, and clinical need for target lesion revascularization (TLR). PCB was superior for coronary restenosis in bare-metal and drug-eluting stents compared with uncoated balloon angioplasty and was noninferior compared with paclitaxel-eluting stents. PCB angioplasty should be considered for treatment of coronary in-stent restenosis. For de novo lesions, PCB plus endothelial progenitor cell capturing stents reduced restenosis and TLR in early reports. Among patients with de novo lesions and diabetes, the combination of PCB plus bare-metal stent revealed similar results in lesions compared with paclitaxel-eluting stents. The early results for PCB in small vessels are also very encouraging. Dual antiplatelet therapy duration may be shorter with PCB angioplasty compared with drug-eluting stents. Nevertheless, the risk for thrombotic vessel occlusion is minimized. Considering peripheral arterial disease, PCB angioplasty for femoropopliteal lesions was superior to uncoated balloon angioplasty. Registries indicate PCB to also be effective in lesions below the knee. Since there is no certain class effect, efficacy and safety have to be demonstrated for different types of PCB for coronary and peripheral interventions.     

Fractured DES with a patent coronary artery: clinical implications

Recently, reports of stent fracture with focal restenosis have suggested that it is another mechanism of in-stent restenosis after implantation of sirolimus-eluting stents. However, the mechanism by which strut disruption occurs remains unknown. Current reports of in-stent restenosis suggest that fracture of drug-eluting stents is different from bare-metal stents, and can progress to restenosis and reocclusion. We report on a patient with a fractured stent in a patent coronary artery that progressed to diffuse neointimal hyperplasia presenting with acute myocardial infarction 2 years after stent placement.     

Results of percutaneous coronary intervention of the unprotected left main coronary artery in 143 patients and comparison of 30-day mortality to results of coronary artery bypass grafting

Percutaneous coronary intervention (PCI) of the unprotected left main coronary artery (LMCA) is controversial. In 143 patients who underwent PCI of the unprotected LMCA, 30-day mortality was compared with predicted cumulative risk-adjusted perioperative surgical mortality based on logistic European System for Cardiac Operative Risk Evaluation. One-year clinical follow-up was completed in all patients. The overall major adverse cardiac event rate at 1 year was 34.3%, reflecting the high-risk profile of the patient population. Twelve patients (8%) experienced an acute myocardial infarction and 16 (11%) underwent target lesion revascularization. In 31 patients (22%) who died during the first year, median logistic European System for Cardiac Operative Risk Evaluation was 30%. Calculated RRs showed significantly lower 30-day mortality using PCI compared with predicted surgical mortality (RR 0.54, 95% confidence interval 0.31 to 0.86). Angiographic follow-up in 90 of the 118 patients alive at 6 months showed binary restenosis of 6% in patients treated with drug-eluting stents versus 29% in patients receiving bare-metal stents (p < or =0.01). In conclusion, PCI for unprotected LMCA disease was associated with acceptable short- and medium-term outcomes in patients at low to intermediate risk of bypass surgery. Mortality remains high in very high-risk patients unsuitable for surgery. However, in selected indications, PCI of the LMCA can offer an alternative to surgery, especially when using drug-eluting stents.     

Late stent thrombosis in brachytherapy: the role of long-term antiplatelet therapy

Advances in percutaneous coronary intervention (PCI) have emerged in the past decade. Stenting has improved upon the limitations of angioplasty, acute vessel closure and restenosis by providing mechanical vascular support, resulting in sustained clinical and angiographic benefit. This has led to greater utilization of the technique, although it is associated with a significant incidence of in-stent restenosis. Neointimal hyperplasia is the pathophysiologic process that leads to in-stent restenosis. Brachytherapy can be effective in reducing the occurrence of this process. Unfortunately, brachytherapy trials have identified the phenomenon of late stent thrombosis as a potentially serious complication of this procedure. Late stent thrombosis is thrombosis that occurs > 30 days after PCI. The risk of thrombosis is increased in patients receiving a new stent in addition to brachytherapy. It also appears to be increased when adjunctive antiplatelet therapy with ticlopidine or clopidogrel is discontinued early. Strategies to prevent late stent thrombosis include the prolonged use of combination antiplatelet therapy in addition to limited placement of new stents in patients treated with brachytherapy for in-stent restenosis.     

Balancing efficacy and safety of drug-eluting stents in patients undergoing percutaneous coronary intervention

Drug-eluting stents reduce the occurrence of in-stent restenosis and the need for subsequent target vessel revascularization compared with bare-metal stents. However, the safety of drug-eluting stents has been called into question because of an apparent increase in late stent thrombosis, a frequently fatal event. A substantial body of research has focused on determining the magnitude of these competing events, often reaching contradictory results even with analyses of the same data. Although larger, adequately powered, randomized trials are needed to fully assess the net clinical effects of drug-eluting stents compared with bare-metal stents, the evidence seems to suggest that the net clinical benefit of drug-eluting stents may outweigh their risks. The evidence is clearer that premature discontinuation of antiplatelet therapy is an important trigger for stent thrombosis; therefore, patients who are candidates for implantation of drug-eluting stents should be screened for their ability to receive and tolerate uninterrupted antiplatelet therapy longer than is necessary with bare-metal stents. The evidence suggests that drug-eluting stents relieve obstructive coronary artery disease, provide durable mechanical results, and do more good than harm, but all patients also should be given antiplatelet and other optimal medical therapies to achieve the best outcomes.     

A randomized comparison of sirolimus-eluting stent implantation with zotarolimus-eluting stent implantation for the treatment of total coronary occlusions: rationale and design of the PRImary Stenting of Occluded Native coronary arteries III (PRISON III) study

Primary intracoronary drug-eluting stent placement after the successful crossing of total coronary occlusions decreases restenosis rate at long-term follow-up compared with bare-metal stent implantation. The PRISON II trial was the first randomized study to show the safety and efficacy of sirolimus-eluting stents in patients with totally occluded native coronary arteries. The sirolimus-eluting stent is superior to the bare-metal stent in treating patients with total coronary occlusions, with significant reduction in angiographic binary in-stent and in-segment restenosis resulting in significantly reduced need for target lesion and target vessel revascularization. Whether sirolimus-eluting stents are superior to other drug-eluting stents in total coronary occlusions is unknown. In this prospective, randomized trial, sirolimus-eluting stent implantation will be compared with zotarolimus-eluting stent implantation for the treatment of total coronary occlusions. A total of 300 patients will be followed for up to 5 years with angiographic follow-up at 8 months. Quantitative coronary analysis will be performed by an independent core laboratory. The primary end point will be in-segment late luminal loss at 8 months angiographic follow-up.     

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.     

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.     

冠脉支架植入术后支架内再狭窄的危险因素分析

目的:探讨冠状动脉支架植人术后支架内再狭窄发生的危险因素。方法:对2006年1月1日至2006年12月31日在我院行冠状动脉支架植入术后行冠状动脉造影随访的121例资料进行了回顾性分析。统计学上采用logis-tic多因素逐步回归分析。结果:多因素logistic回归分析显示再狭窄与患者是否有糖尿病,是否吸烟以及第二次冠脉介入治疗前LDL-C水平成显著正相关,其相对危险度(RR)分别为11.55、5.48和12.60;而与支架是否为药物涂层成负相关,RR为0.01。结论:糖尿病患者为支架术后再狭窄的的高危人群,药物支架可减少再狭窄的发生。对于支架植入术后的患者,戒烟以及控制LDL-C的水平是减少支架内再狭窄的关键因素。     

Kissing drug-eluting balloons for the treatment of unprotected distal left main bifurcation drug-eluting stent restenosis

The advent of drug-eluting stents (DES) associated with improvements in interventional techniques, encouraged the use of percutaneous coronary intervention (PCI) for unprotected left main (ULM) stenosis because of the lower need of repeat revascularization compared to the bare-metal stents (BMS). Nevertheless, ULM DES in-stent restenosis (ISR) continues to occur. The choice of treatment strategy (medical treatment, repeated PCI, or coronary artery bypass graft) for ULM DES-ISR depends primarily on several clinical and angiographic factors, making optimal patient selection crucial in the appropriate treatment of ULM-ISR lesions and achievement of favorable long-term outcomes. We describe in this report a successful modern approach to manage a distal ULM DES-ISR following a 2-stent strategy, consisting in the kissing inflation of two DEBs in both branches of the bifurcation.     

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.     

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.     

Usefulness and safety of percutaneous coronary interventions for cardiac transplant vasculopathy

Late morbidity and death as a result of progressive coronary vascular obliteration remains a major unsolved problem after orthotopic heart transplantation. Various percutaneous catheter intervention (PCI) methods have been used to treat transplant coronary artery disease (CAD), but few reports have assessed the longitudinal results of these procedures. Of 1,440 cardiac transplant patients at University of California, Los Angeles, Medical Center, treated between 1984 and 2004, 65 patients who had undergone orthotopic heart transplantation underwent PCI on a total of 156 coronary artery lesions because of transplant CAD between July 1993 and August 2004. The procedural success rate was 93%. Angiographic follow-up was available for 42 patients and 101 lesions 9.5 +/- 5.8 months after PCI. The global restenosis rate was 36%. Multivariate analysis was used to assess 49 clinical, angiographic, and immunologic variables per lesion. The use of a cutting balloon increased the risk of restenosis (odds ratio 11.5, p <0.01) and the use of stents decreased the risk of restenosis (odds ratio 0.34, p <0.05) compared with other PCI methods. The restenosis rate with drug-eluting stents was 19%, lower than that with bare metal stents (31%). Of the 65 patients, 20 (31%) died within 1.9 +/- 1.8 years after PCI. The actuarial survival rate was 56% at 5 years after the first PCI. In conclusion, although the restenosis rate after PCI was higher than that in nontransplant patients with CAD, the immediate and long-term results were acceptable in this high-risk population. Despite the intense inflammation associated with transplant CAD, drug-eluting stents appeared to reduce the occurrence of restenosis. Compared with historical controls, PCI may also improve the actuarial survival rate of patients undergoing orthotopic heart transplantation.     

Drug-eluting stents and other anti-restenosis devices

Restenosis remains as the main limitation of percutaneous coronary intervention, even in the era of coronary stents. Recently, drug-eluting stents have been shown to reduce significantly both the rate of in-stent restenosis and the need for subsequent revascularization procedures compared with bare-metal stents. At present, these beneficial effects have been demonstrated mainly with Cypher (Cordis Corporation) and Taxus (Boston Scientific) stents. They persist for at least 3 years after implantation. Although the results of some complex clinical angiographic studies are still awaited, all the indications suggest that use of this type of stent will become standard in percutaneous coronary interventions in the future. With regard to other techniques, intracoronary brachytherapy is effective only for the treatment of in-stent restenosis. The recent withdrawal from the market of brachytherapy catheters means that the technique has effectively disappeared from the interventional cardiologist's armamentarium, at least in our setting. Other devices, especially rotational atherectomy catheters and cutting balloons, will survive in the era of drug-eluting stents as they facilitate stent implantation in particularly complex lesions.     

Drug-eluting stents: from randomized trials to the real world

Drug-eluting stents have been developed to prevent in-stent restenosis following percutaneous coronary revascularization. In a number of randomized trials, polymer-coated sirolimus- and paclitaxel-eluting stents have been proven to markedly reduce the incidence of angiographic restenosis and repeat revascularization when compared to bare metal stents. Effectiveness of sirolimus-eluting stents in the prevention of restenosis has been confirmed in many subsets of patients and lesions not included in randomized trials, such as in-stent restenosis, chronic total occlusion, acute myocardial infarction, and others. Very promising data in the real world are emerging for utilization of paclitaxel-eluting stents as well. Other drug-eluting stents gave less brilliant results or even true failures, whilst a number of new drugs and stent platforms are under clinical or preclinical evaluation. In this review we describe the main clinical trials on drug-eluting stents, and the most recent informations derived from observational studies and registries. Moreover, preliminary results on new drug-eluting stents are summarized.     

冠脉支架植入术后支架内再狭窄的危险因素研究

目的对冠脉支架植入术后的支架内再狭窄危险因素进行研究。方法在2011年7月-2013年7月期间,我院收治冠脉支架植入术患者120例,对该120例患者术后支架内的再狭窄危险因素进行研究,并采取Logistic多因素分析再狭窄的危险因素。结果通过术后患者危险因素研究可知,与患者的胆固醇、术前狭窄、是否吸烟、有糖尿病及高血压等因素有关,与支架有无药物涂层也有关,表现为负相关,危险度是0.01。结论对糖尿病及高血压患者来说,实施支架植入术之后,出现再狭窄症状的几率增加。同时,冠脉支架患者对危险因素应采取预防措施,如戒烟,避免再狭窄情况出现,提高患者的生存质量。