The long-term value of sirolimus- and paclitaxel-eluting stents over bare metal stents in patients with diabetes mellitus.

AIMS: To investigate the outcome of a real world diabetic patient cohort treated with bare metal stents (BMS), sirolimus-, or paclitaxel-eluting stents (SES and PES, respectively). Due to the different mechanisms of action of both drugs it is currently unknown which device is the best option to treat these high-risk patients. METHODS AND RESULTS: The study compares the 2-year clinical outcome of 708 consecutive diabetic patients (25% insulin treated) treated with either a BMS (n = 252), a SES (n = 206), or a PES (n = 250), as part of the RESEARCH and T-SEARCH registries. Target vessel revascularization was 19.5% in the BMS group, vs. 15.3% in the SES group and 9.7% in the PES group. PES (21.2%), but not SES (28.9%), were superior to BMS (29.7%) in reducing major adverse cardiac events. After propensity analyses, none of the differences remained significant. The incidence of stent thrombosis (ST) was high in both DES groups. CONCLUSION: There was a trend towards a more favourable outcome associated with the use of PES over BMS. There was no significant difference between SES and PES in each of the clinical endpoints, and neither in the NIDDM patients, which are hypothesized to be better-off with PES.     

Concurrent implantation of sirolimus- and paclitaxel-eluting stents in the same vessel.

OBJECTIVE: To assess the safety and efficacy of concurrent implantation of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents in the same coronary artery. BACKGROUND: When it is impossible to deliver multiple drug eluting stents (DES) of the same type, the operator must opt to implant a different DES or a bare metal stent. There are currently no published data evaluating this approach. METHODS: We identified all cases in which one or more SES and PES were implanted in either the same lesion or adjacent segments of the same vessel during a single procedure between March 2003 and March 2005. Endpoints analyzed were; in-hospital major adverse cardiac events (MACE), and follow-up MACE (including stent thrombosis). RESULTS: We identified 44 patients with 89 lesions. This was a complex cohort of patients with a median of 3.5 stents implanted, 3 lesions and 2 vessels treated and a median stent length implanted of 80.5 mm, while 83% of the lesions were type B2/C. Eight patients had peri-procedural myocardial infarction. During follow-up; 1 cardiac death occurred, no patients had a myocardial infarct or stent thrombosis, 11 underwent target lesion and vessel revascularization (25%) and 13 had a major adverse cardiac event (29.5%). CONCLUSIONS: In this cohort of patients, the concurrent use of SES and PES in the same vessel was associated with outcomes in keeping with the complexity of disease treated. Our data show that it is not unreasonable to implant different DES in the same vessel, although we would not advocate this as routine practice.     

Efficacy and safety of zotarolimus-eluting stents compared with sirolimus-eluting stents in patients undergoing percutaneous coronary interventions — A meta-analysis of randomized controlled trials

Background

Whether ZES can further improve angiographic and clinical outcomes compared to SES still remains uncertain.

Objectives

The aim of this study was to assess the efficacy and safety of zotarolimus-eluting stents (ZES) compared with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary interventions (PCI).

Methods

Major electronic information sources were explored for randomized controlled trials comparing ZES with SES among patients undergoing PCI during at least 9 months follow-up. The primary efficacy outcomes were target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE); safety outcomes were stent thrombosis (ST), myocardial infarction (MI), and cardiac death.

Results

Seven comparative studies were identified (a total of 5983 patients). When compared with ZES at 12-month follow‐up, SES significantly reduced risk of MACE (relative risk [RR]: 0.74, 95% confidence interval [CI]: 0.61 to 0.89, p = 0.002), and TLR (RR:0.39; 95% CI: 0.29 to 0.52; p < 0.00001), without significant differences in terms of TVR (RR:0.68, 95% CI: 0.38 to 1.20; p = 0.18), ST (RR:0.71; 95% CI: 0.39 to 1.31; p = 0.28), cardiac death (RR:0.83; 95% CI: 0.49–1.42, p = 0.50) or MI (RR:1.08; 95%CI: 0.80 to 1.45; p = 0.62).

Conclusions

At 12-month follow-up, SES are superior to ZES in reducing the incidences of TLR and MACE in patients undergoing PCI, without significant differences in terms of TVR, ST, cardiac death, and MI.     

同种和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄有效性的系统评价

目的评价同种药物洗脱支架和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄的有效性。方法计算机检索Pub Med、OVID、Embase、Cochrane图书馆、万方数据库、中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、维普数据库(VIP),收集同种和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄的临床资料,共纳入10项研究,1680名患者,使用Rev Man5.2软件进行系统评价。检索时间为各大数据库建库至2015年10月。结果在治疗冠状动脉药物洗脱支架内再狭窄时,采用不同药物洗脱支架可降低靶病变血运重建率(OR=0.73,95%CI为0.55~0.96,P=0.02)和主要不良心血管事件发生率(OR=0.72,95%CI为0.54~0.96,P=0.03)。两组间的病死率(OR=1.03,95%CI为0.49~2.16,P=0.95)和心肌梗死发生率(OR=0.59,95%CI为0.24~1.41,P=0.23)无统计学差异。结论对于药物洗脱支架内再狭窄患者,再次植入不同药物洗脱支架比植入同种支架更获益。     

Early vascular response to overlapped paclitaxel-eluting stents in swine coronary arteries

BACKGROUND: The early response to the TAXUS Express2 paclitaxel-eluting stent (PES) system was compared to the response to the Express2 bare metal stent (BMS) system in porcine arteries. METHODS: Swine coronary arteries were implanted with overlapping PES or BMS and examined at 1, 2, 4, 10, and 20 days postimplantation using scanning electron microscopy or light microscopy. RESULTS: Vascular healing in terms of strut coverage, reendothelialization, degree of inflammation, and absence of thrombus was equivalent in both groups from 1 to 20 days. Interstrut member spaces were unaffected by stent deployment and remained covered with endothelium from Day 1. In both groups at 2 days, small patches of endothelial cells covered approximately 5-10% of the stent surface. At 4 days, endothelial cell coverage progressed to nearly 50% in both groups. After 10 days, endothelial cell strut coverage was nearly complete (>90%), with regions of incomplete coverage located primarily in strut overlap regions in both groups. BMS exhibited a fibrocellular neointima and no parastrut fibrin, whereas PES exhibited a developing but immature fibrocellular neointima and prominent parastrut fibrin. By Day 20, an endothelialized neointima was present in both groups, with comparable coverage of proximal and distal stented regions. The neointima of PES was more fibrocellular and parastrut fibrin was still comparable to that at 10 days. CONCLUSION: Early vascular response was comparable for both PES and BMS, with similar rates of reendothelialization, limited inflammatory response, and absence of thrombus, but differed parastrut fibrin clearance and neointimal maturation rate.     

Cardiogenic shock caused by simultaneous subacute stent thrombosis after implantation of sirolimus-eluting stents

Stent thrombosis is a feared complication of percutaneous coronary intervention, although there is a low incidence of thrombotic events following drug-eluting stent implantation. We report a case with cardiogenic shock complicated by acute myocardial infarction due to simultaneous subacute stent thrombosis occurring 3 days after implantation of two sirolimus-eluting stents in the proximal left anterior descending artery (LAD) and in the proximal right coronary artery (RCA).     

药物涂层支架预防冠脉介入术后再狭窄188例临床研究

目的观察药物涂层支架预防冠脉介入术后再狭窄效果.方法根据443例冠心病患者病变部位及复杂程度,分别置入药物涂层支架和普通支架(裸支架),并随访1～28个月 .结果除5例行涂层支架者因支架远端夹层形成而再次置入支架外, 手术即刻成功率100% ,术后冠脉造影显示病变残余率(6±4)%,支架完全覆盖病变,血流TIMI3级.仅1例行裸支架者因支架置入血管发生急性闭塞而死亡.随访期间,发生与支架置入有关的再狭窄33例 ,其中裸支架置入32例(64处),药物涂层支架置入仅1例(3处).药物涂层支架置入的再狭窄率(1.23%)明显低于裸支架置入(13.82%),P＜0.01 .结论药物涂层支架置入可显著降低冠脉介入术后再狭窄率.     

Different effects of thiazolidinediones on target vessel revascularization with bare metal stents: a meta-analysis

ObjectiveThiazolidinediones (TZDs) are used in patients with Type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on target vessel revascularization. The aim of this meta-analysis is to evaluate the effect of TZDs on repeat target vessel revascularization following percutaneous coronary intervention.Research design and methodsWe searched Medline, EMBASE, Cinahl, and the Cochrane Database from earliest available date through December 2007. Criteria for inclusion in our meta-analysis included the use of randomized control trial and the availability of target vessel revascularization. Relative risks (RRs) with 95% confidence intervals (CIs) of target vessel revascularization (TVR) and restenosis were estimated using a fixed-effects meta-analysis of seven randomized controlled trials (n=347, including 178 receiving pioglitazone and 169 receiving rosiglitazone).ResultsOne hundred seventy-eight patients were treated with pioglitazone, and 169 were treated with rosiglitazone. Pioglitazone is associated with a significantly lower risk of target vessel revascularization or restenosis (TVR: n=37/96 vs. 7/94; RR, 5.91; 95% CI, 3.00–11.7; P<.0001, restenosis: n=42/96 vs. 8/94; RR, 6.48; 95% CI, 3.37–12.4; P<.0001). Rosiglitazone had no effect on target vessel revascularization (n=56/131 vs. 51/124; RR, 1.11; 95% CI, 0.63–1.96; P=.793).ConclusionsPioglitazone is associated with a significantly decreased risk of target vessel revascularization, but rosiglitazone does not reduce the risk of target vessel revascularization following percutaneous coronary intervention.     

Nine-year clinical outcomes of drug-eluting stents vs. bare metal stents for large coronary vessel lesions

Objectives To evaluate the very long-term safety and effectiveness of drug-eluting stents (DES) compared to bare-metal stents (BMS) for patients with large coronary vessels. Methods From April 2004 to October 2006, 2407 consecutive patients undergoing de novo lesion percutaneous coronary intervention with reference vessel diameter greater than or equal to 3.5 mm at Fu Wai Hospital in Beijing, China, were prospectively enrolled into this study. We obtained 9-year clinical outcomes including death, myocardial infarction (MI), thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE, the composite of death, MI, and TVR). We performed Cox’s proportional-hazards models to assess relative risks of all the outcome measures after propensity match. Results After propensity scoring, 514 DES-treated patients were matched to 514 BMS-treated patients. The patients treated with BMS were associated with higher risk of TLR (HR: 2.55, 95% CI: 1.520–4.277, P = 0.0004) and TVR (HR: 1.889, 95% CI: 1.185–3.011, P = 0.0075), but the rates of death/MI and MACE were not statistically different. All Academic Research Consortium definition stent thrombosis at 9-year were comparable in the two groups. Conclusions During long-term follow-up through nine years, use of DES in patients with large coronary arteries was still associated with significant reductions in the risks of TLR and TVR.     

不同药物洗脱支架在冠状动脉弥漫性长病变中的2年随访结果比较

目的评价在冠状动脉弥漫性长病变中使用重叠西罗莫司（雷帕霉素）洗脱支架（SES）与重叠紫杉醇洗脱支架（PES）的疗效及安全性。方法研究入选冠状动脉弥漫性长病变患者197例,分别接受重叠SES（CypherTM,75例,110处病变）或PES（TaxusTM,122例,177处病变）。比较两组随访6个月时造影及随访2年时的临床结果。结果随访6个月时造影结果表明,SES组最小管腔直径显著高于PES组（P=0.013）;晚期管腔丢失、再狭窄百分比和二元再狭窄率显著低于PES组（P均〈0.05）。2年临床随访结果显示,SES组总死亡率、靶病变血运重建、靶血管血运重建及主要不良心脏事件的发生率显著低于PES组（P均〈0.05）。多因素回归分析显示,相较于PES,SES是随访2年时总死亡（OR=0.20,95%CI：0.05~0.83,P=0.027）、靶病变重建（OR=0.26,95%CI：0.10~0.73,P=0.010）和主要不良心脏事件（OR=0.38,95%CI：0.18~0.82,P=0.014）的独立保护性预测因素。结论在冠状动脉弥漫性长病变治疗中,相较于重叠使用PES,重叠SES显著改善了6个月时的造影随访结果,并且该结果能转化成为更佳的2年临床随访结果。     

Sirolimus-eluting Stent for the Treatment of Small Coronary Artery Lesions:Comparison between Cypher and Firebird Stent

Objectives To evaluate the effectiveness of firebird stent for the treatment of coronary de novo lesion compared with cypher stent. Methods Ninety-one consecutive patients with 156 lesions who underwent coronary cypher (n = 68 lesions) and firebird (n = 88 lesions) implantation, quantitative coronary angiography (QCA) was performed at the time of stent implantation and subsequently at 8 months post-stenting. Small vessel disease was defined as ≤2.5 mm of reference vessel diameter measured by QCA. Major adverse cardiac events (MACE) including death, thrombosis, nonfatal myocardial infarction and target lesion revascularization (TLR) were compared between the two groups. Results Baseline clinical characteristics and angiographic parameters were similar between the two groups. Seven-month angiographic follow-up, the late loss was not different between the two groups (0.14 ± 0.38 mm vs 0.13 ± 0.17 mm, P > 0.05). Similarly, overall thrombosis rate were similar in both groups (1.5% vs 1.1%, P > 0.05). However, in-stent restenosis as well as in-segment restenosis rate were significantly higher in cypher group than that in firebird group (4.4% vs 0% and 19.1% vs 3.4%, P = 0.047 and P = 0.001 respectively). TLR was also higher in the cypher group (10.3% vs 2.3%, P = 0.033) compared with firebird group. Conclusions In this small sample size, non-randomized study, the data indicated that implantation of firebird stent for the treatment of small coronary lesion showed more favorable results in respective of restenosis compared with cypher stent implantation. A multi-center, large-sample size, randomized study, therefore, may be warranted.     

The impact of triple anti-platelet therapy for endothelialization and inflammatory response at overlapping bioabsorbable polymer coated drug-eluting stents in a porcine coronary model

Background

This study was conducted to evaluate the endothelialization and the inflammatory responses depending on the administration duration of triple anti-platelet therapy at overlapping bioabsorbable polymer coated biolimus-eluting stents (BESs) in a porcine coronary model.

Methods

We successfully deployed 36 overlapping BESs for the left anterior descending coronary and left circumflex artery or right coronary artery in 18 non-injured pigs. Total pigs were divided into 3 groups (12 overlapping stents of 6 pigs in each group) as follows: group I received aspirin 100 mg and clopidogrel 75 mg daily for 8 weeks, group II received aspirin 100 mg and clopidogrel 75 mg daily for 8 weeks and cilostazol 200 mg daily for initial 4 weeks, and group III received aspirin 100 mg, clopidogrel 75 mg, and cilostazol 200 mg daily for 8 weeks. Follow-up coronary angiograms and histomorphometric and histopahtologic analyses at overlapping and non-overlapping segments were performed respectively.

Results

Inflammation score was similar between overlapping and non-overlapping segments in all pigs (1.2 ± 0.33 vs. 1.1 ± 0.17, p = 0.117). The neointima area (NA) and percent area stenosis (%AS) at overlapping segments were not significantly different among the 3 groups. However, at non-overlapping segments, NA and %AS in group III were significantly smaller than those in group I (2.3 ± 0.50 mm² vs. 1.8 ± 0.43 mm², p = 0.037; 48.9 ± 12.85% vs. 37.7 ± 9.08%, p = 0.031).

Conclusions

Our study shows that BES appears to be reliable on the inflammatory response at overlapping segments as well as non-overlapping segments. Long-term administration of cilostazol is more effective in reducing neointimal formation at non-overlapping segments of BESs in a porcine coronary model.     

雷公藤内酯醇洗脱支架与雷帕霉素洗脱支架对冠状动脉支架内再狭窄作用的对比研究

目的 比较雷公藤内酯醇洗脱支架与西罗莫司（sirolimus,雷帕霉素）洗脱支架预防冠状动脉支架植入术后再狭窄的作用.方法 选用杂种幼猪30只,随机分成裸支架组、雷公藤内酯醇洗脱支架组和西罗莫司洗脱支架组,每组各植入支架10枚.术后28 d,进行冠状动脉造影、组织病理检查以及免疫组化检测血管平滑肌细胞中增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）.结果 雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组支架内最小内径相似（P＞0.05）,均大于裸支架组（P＜0.01）;雷公藤内酯醇洗脱支架组新生内膜面积与西罗莫司洗脱支架组相似（P＞0.05）,均小于裸支架组（P＜0.01）.雷公藤内酯醇洗脱支架组与西罗莫司洗脱支架组的PCNA阳性细胞数相似（P＞0.05）,均少于裸支架组（P＜0.01）.结论 雷公藤内酯醇洗脱支架能抑制平滑肌细胞增殖,其预防冠状动脉支架内再狭窄的作用与西罗莫司洗脱支架相似.     

Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial.

AIM: Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2). METHODS AND RESULTS: A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52). CONCLUSION: The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.     

Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial.

AIMS: Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial. METHODS AND RESULTS: The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group. CONCLUSION: SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.     

CYPHER药物洗脱支架治疗支架内再狭窄的临床疗效

目的:探讨CYPHER药物洗脱支架治疗支架内再狭窄的经验及临床疗效.方法:9例支架内再狭窄患者接受了12枚CYPHER药物洗脱支架治疗,其中右冠状动脉病变4例,前降支病变7例,左旋支病变1例.结果:12处支架内再狭窄病变均成功放置药物支架,手术成功率100%.所有患者临床症状明显改善,无并发症发生.所有患者于术后6个月复查冠状动脉造影,无一例发生再狭窄.结论:CYPHER药物洗脱支架治疗支架内再狭窄安全、有效、可行.     

Differential healing response attributed to culprit lesions of patients with acute coronary syndromes and stable coronary artery after implantation of drug-eluting stents: An optical coherence tomography study

Background

Pathology studies have shown delayed arterial healing in culprit lesions of patients with acute coronary syndrome (ACS) compared with stable coronary artery disease (CAD) after placement of drug-eluting stents (DES). It is unknown whether similar differences exist in-vivo during long-term follow-up. Using optical coherence tomography (OCT), we assessed differences in arterial healing between patients with ACS and stable CAD five years after DES implantation.

Methods and results

A total of 88 patients comprised of 53 ACS lesions with 7864 struts and 35 stable lesions with 5298 struts were suitable for final OCT analysis five years after DES implantation. The analytical approach was based on a hierarchical Bayesian random-effects model. OCT endpoints were strut coverage, malapposition, protrusion, evaginations and cluster formation. Uncovered (1.7% vs. 0.7%, adjusted p = 0.041) or protruding struts (0.50% vs. 0.13%, adjusted p = 0.038) were more frequent among ACS compared with stable CAD lesions. A similar trend was observed for malapposed struts (1.33% vs. 0.45%, adj. p = 0.072). Clusters of uncovered or malapposed/protruding struts were present in 34.0% of ACS and 14.1% of stable patients (adj. p = 0.041). Coronary evaginations were more frequent in patients with ST-elevation myocardial infarction compared with stable CAD patients (0.16 vs. 0.13 per cross section, p = 0.027).

Conclusion

Uncovered, malapposed, and protruding stent struts as well as clusters of delayed healing may be more frequent in culprit lesions of ACS compared with stable CAD patients late after DES implantation. Our observational findings suggest a differential healing response attributable to lesion characteristics of patients with ACS compared with stable CAD in-vivo.