西罗莫司洗脱支架(CypherTM)治疗支架内再狭窄

目的探讨CypherTM药物洗脱支架治疗支架内再狭窄的安全性和有效性。方法11例支架内再狭窄患者共置入CypherTM药物洗脱支架15枚,所有患者随访6个月,并于术后6个月复查冠状动脉造影。结果介入手术成功率100%,未发生与介入治疗相关的并发症。术后所有患者临床症状明显改善,6个月复查冠状动脉造影,无一例发生再狭窄。结论西罗莫司(雷帕霉素)洗脱支架治疗支架内再狭窄有很强的安全性、有效性。     

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.     

Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas.

OBJECTIVE: To assess the effect of irinotecan-eluting stents (IS) on neointimal growth in the aortas of hypercholesterolemic rabbits and to determine other local histopathological effects such as necrosis, fibrin, and inflammatory reaction. METHODS: Phosphorylcholine-coated stents were deployed in the aortas of hypercholesterolemic rabbits. Group 1 (control; n = 8) received unloaded stents, group 2 (n = 7) and group 3 (n = 9) received IS with 0.046 mg and 1.29 mg of irinotecan, respectively. Eight weeks after implantation the rabbits were killed. Neointimal thickness (NT) was assessed by morphometry. Semiquantitative injury score (from 0 to 3+) was used to analyze inflammatory infiltrate, fibrin deposits, and necrosis in the stented segments. RESULTS: NT was reduced only in high-doses IS (G1, 167.4 +/- 20.8 mu; G2, 170.24 +/- 21.2 mu; G3, 111.56 +/- 12.7 mu; P < 0.05, G3 vs G1 and G2). Necrosis decreased significantly with IS [1.00 +/- 0.10 in G1 to 0.33 +/- 0.07 and 0.02 +/- 0.01 in G2 and G3, respectively] only in the media layer. The inflammatory infiltrate was present in the three layers of aortas from G1, but only decreased significantly in the intimae layer of the high-dose group [1.50 +/- 0.15 in G1 vs 1.00 +/- 0.18 in G3, P < 0.05]. CONCLUSION: Stents loaded with high-dose irinotecan inhibit NT in the aortas of hypercholesterolemic rabbits. This effect was accompanied by decreased inflammatory infiltrate and media necrosis.     

Advantages and disadvantages of biodegradable platforms in drug eluting stents

Coronary angioplasty with drug-eluting stent(DES)implantation is currently the most common stent procedure worldwide.Since the introduction of DES,coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced.However,the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to baremetal stent(BMS)implantation.Several factors have been associated with very late stent thrombosis after DES implantation,such as delayed healing,inflammation,stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers,which were essential to allow the elution of the immunosuppressive drug in the first DES designs.The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug,after which a BMS remains in place.Several DES designs with biodegradable(BIO)polymers have been introduced in preclinical and clinical studies, including randomized trials.In this review,we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.     

雷帕霉素洗脱支架临床应用分析

目的　评价雷帕霉素洗脱支架 (CypherTM)的安全及近期有效性。方法　回顾分析 112例接受CypherTM 支架置入术患者的即刻疗效和临床随访结果。结果　 112例患者共处理 173处病变 ,置入支架 2 2 7枚 ,其中 132处病变置入15 9枚CypherTM支架。 2处严重钙化病变需辅以高压球囊才充分扩张 ,1处支架近端发生内膜撕裂。其余全部成功置入 ,手术过程及住院期间无严重并发症发生 ,成功率 98 1%。10 4例患者随访 3～ 17个月 ,平均 (7 2± 4 0 )个月 ,无心源性死亡和心肌梗死发生 ,9例患者心绞痛再发 ,其中 5例为普通金属支架内的再狭窄 ,4例为其他分支的新病变。 112例患者中共 2 8例复查了冠状动脉造影 ,CypherTM支架内均无再狭窄。结论　CypherTM支架近期安全有效。     

Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels.

AIMS: Sirolimus- and paclitaxel-eluting stents effectively reduce restenosis in small coronary vessels. The relative efficacy of these drug-eluting stents in this high-risk subset is not known. METHODS AND RESULTS: A total of 360 patients undergoing percutaneous coronary intervention for de novo lesions in native coronary vessels with a diameter of <2.80 mm received randomly paclitaxel-eluting stents (n=180) or sirolimus-eluting stents (n=180). The primary endpoint was in-stent late luminal loss. Secondary endpoints were angiographic restenosis and need of target lesion revascularization. The study intended to show that the paclitaxel-eluting stent is not inferior to the sirolimus-eluting stent with respect to the primary endpoint. The non-inferiority margin was set at 0.16 mm. Follow-up angiography was performed in 87% of the patients. In-stent late luminal loss in the paclitaxel-eluting stent group was 0.32 mm (upper 95% boundary, 0.42 mm), which was greater than that in the sirolimus-eluting stent group, failing to show the non-inferiority of the paclitaxel-eluting stent to the sirolimus-eluting stent (P>0.99). Angiographic restenosis was found in 19.0% of the lesions in the paclitaxel-eluting stent group and 11.4% of the lesions in the sirolimus-eluting stent group (P=0.047). Target lesion revascularization was performed in 14.7% of the lesions treated with paclitaxel-eluting stents and 6.6% of the lesions treated with sirolimus-eluting stents (P=0.008). CONCLUSION: The paclitaxel-eluting stent is associated with a greater late luminal loss and is less effective in reducing restenosis in small coronary vessels than the sirolimus-eluting stent.     

Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks.

AIMS: The addition of drug elution to coronary stents plays an integral role in coronary restenosis prevention. The present study was undertaken to determine the mechanism of action and the in vitro and in vivo efficacy of zotarolimus, a new chemical entity designed specifically for elution from phosphorylcholine (PC)-coated stents, for the reduction of neointimal hyperplasia in porcine coronary arteries. METHODS AND RESULTS: In vitro studies of Zotarolimus bound to FKBP-12 potently inhibited smooth muscle cells (SMCs) and endothelial cell (EC) proliferation. Twenty PC-only and 20 stents eluting zotarolimus 10 microg/mm were implanted in the coronary arteries of 20 domestic juvenile swine. After 28 days, zotarolimus stents exhibited less area stenosis (22.4+/-8.6 vs. 35.7+/-13%, P = 0.01), less neointimal area (1.69+/-0.55 vs. 2.78+/-1.07 mm(2), P = 0.01), less neointimal thickness (0.25+/-0.07 vs. 0.38+/-0.13 mm, P = 0.01), and greater lumen area (6.07+/-1.39 vs. 5.02+/-1.3 mm2, P = 0.01). All arteries in both the polymer-only and polymer/drug stent showed near-complete healing and minimal toxicity. Zotarolimus did not affect the extrastent segments nor alter the overall artery size (external elastic lamina cross-sectional area 9.18+/-1.19 vs. 9.06+/-1.28 mm2, P = 0.7). CONCLUSION: Zotarolimus binds to FKBP-12 and in vitro inhibits SMC and EC proliferation. Zotarolimus applied to PC-coated stents reduces neointima in the swine coronary model after 28 days. These results suggest potentially promising human clinical application for coronary stenting with this polymer/drug combination.     

Sirolimus-eluting stents and calcified coronary lesions: clinical outcomes of patients treated with and without rotational atherectomy.

This study examined the outcomes of patients who underwent sirolimus-eluting stent (SES) implantation for the treatment of heavily calcified coronary lesions (HCCL) with and without the use of rotational atherectomy (rotablator). We investigated 150 consecutive patients with angiographic evidence of HCCL who underwent SES implantation. Sixty-nine patients underwent SES implantation without the need of rotablator (SES), and 81 patients required rotational atherectomy to modify the plaque and facilitate the delivery of the stent (SES + rotational atherectomy). Clinical success was equivalent in both groups (>98%) and there were no in-hospital outcome differences. At 6 months, the target lesion revascularization rate was 4.9% in SES vs. 4.2% in SES + rotational atherectomy groups, respectively (P = NS). Mortality at 6 months was 7.9% in the SES group vs. 6.8% in the SES + rotational atherectomy group (P = NS). SES performs well in patients with complex HCCL, with a relative low event rate. Lesions requiring rotational atherectomy to facilitate dilation and stenting had similar outcomes after SES implantation to those that could be stented without the need for rotablator.     

Clinical impact of drug-eluting stents in an unselected population of diabetic patients

BACKGROUND: Drug-eluting stents (DES) have been shown in randomized trials to reduce clinical events in diabetic patients. Our aim was to determine whether these clinical results are applicable in an unselected population of patients with non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). METHODS: We studied 440 consecutive patients (271 NIDDM and 169 IDDM) who underwent percutaneous coronary intervention, divided into 2 cohorts: Group A (1998-2000): 220 patients with bare metal stents, and Group B (2002-2004): 220 patients with drug-eluting stents. We analyzed major coronary adverse events (death, nonfatal acute myocardial infarction, and target lesion revascularization) over a mean follow-up of 18+/-15 months. RESULTS: Group B had more patients who were insulin-dependent (44.5 versus 32.3% p<0.001) or had hypertension (64.5 versus 54.1%; p=0.02), a lower left ventricular ejection fraction (53.89 versus 56.8%; p=0.04), more complex lesions (B2/C) (82.7 versus 62.3%; p<0.001), more treated lesions (1.40 versus 1.26; p<0.001), more stents implanted (1.69 versus 1.15; p<0.0001), and more patients treated with abciximab (76.8 versus 42.7%; p<0.0001). During the follow-up, Group B had fewer major adverse coronary events (11.7 versus 27.9%; p<0.001) and a reduction in target lesion revascularization (3.9 versus 17.2%; p<0.001), with no differences in death or myocardial infarction. Both groups experienced a significant reduction in events (NIDDM: 8.1 versus 26.7%; p<0.001 and IDDM: 16 versus 31.9%; p=0.016). Multivariate regression analysis showed the use of drug-eluting stents to be in direct relation with event-free survival (odds ratio [OR]: 3.37; 95% confidence interval [CI], 1.44-7.90; p=0.005). CONCLUSION: Despite the worse angiographic characteristics, the use of DES reduced clinical events, particularly target lesion revascularization.     

Local delivery of nadroparin for the prevention of neointimal hyperplasia following stent implantation: results of the IMPRESS trial. A multicentre, randomized, clinical, angiographic and intravascular ultrasound study.

BACKGROUND: We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS: In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION: Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.     

Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients.

AIMS: Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents. METHODS AND RESULTS: In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years. CONCLUSION: Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.     

Randomized trial of rapamycin- and paclitaxel-eluting stents with identical biodegradable polymeric coating and design.

Aims: This prospective, randomized study sought to directly compare the performance of paclitaxel and rapamycin on an otherwise identical, polymer-coated drug-eluting stent (DES) platform. METHODS AND RESULTS: Stents with identical design and biodegradable polymeric coating that elute either rapamycin or paclitaxel over a 2 months time period were utilized. In this pilot trial that included 91 patients, both stent platforms proved safe with no case of death, Q-wave myocardial infarction or stent thrombosis within a 9 months follow-up period. Late-lumen loss was markedly greater in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group (0.96 +/- 0.75 vs. 0.33 +/- 0.46 mm, P < 0.0001). Likewise, the rate of angiographic restenosis was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [39.0 vs. 12.2%; relative risk (RR) 3.20 (95% confidence interval, 1.29-7.92), P = 0.005]. Concomitantly, the need for target lesion revascularization was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [26.7 vs. 8.7%; RR 3.07 (1.07-8.80), P = 0.02]. CONCLUSION: The results of this clinical trial that is the first to directly compare the performance of paclitaxel and rapamycin on a DES platform otherwise identical in design and polymeric coating imply that rapamycin is more effective for the prevention of coronary restenosis on a DES platform with mid-term drug release and less dependent on release kinetics than paclitaxel. Thus, to ensure efficacy, drug release from a paclitaxel-coating stent platform must be prolonged and well controlled to achieve results that are comparable with the FDA-approved paclitaxel-eluting stent platform.     

Late vascular response at the edges of sirolimus analogous-eluting stents in diabetic patients: An intravascular ultrasound study.

INTRODUCTION: Vascular response at edges of drug-eluting stents is still not well established, particularly in diabetic patients who are prone to aggressive atherosclerosis progression. Recently, Biolimus and Zotarolimus have demonstrated potent antiproliferative effects. OBJECTIVE: To compare the vascular responses at edges of sirolimus analogous-eluting stents in patients with and without diabetes, using intravascular ultrasound (IVUS). METHODS: 306 edges were analyzed in 153 patients treated with drug-eluting stents and divided in: diabetics (122 edges) and nondiabetics (166 edges). IVUS was performed postintervention and at 6-month follow-up and included 5 mm distal and proximal to the stented segment. Vessel, lumen, and plaque volumes were calculated. Volume variation (follow-up minus basal) was also calculated. Edge restenosis was defined as obstruction >50%. RESULTS: Baseline characteristics were similar between groups. In both groups the entire lesion length was covered (stent length/lesion length ratio was 1.5 for both groups). There were no differences in edge volumes and restenosis rate between the groups. Among diabetics, there was no significant volume variation. However, in nondiabetic patients there was significant increase in vessel volume in proximal (from 67.1 +/- 22 mm(3) to 72.2 +/- 25 mm(3): P = 0.02) and distal (from 54.4 +/- 22 mm(3) to 59.8 +/- 22 mm(3): P = 0.001) edges. CONCLUSION: Nondiabetic patients showed a significant positive vascular remodeling in proximal and distal edges of sirolimus analogous-eluting stent. This vascular mechanism was not observed in diabetic patients. Although different vascular responses were observed, restenosis rates were equivalent between the 2 groups at 6-month follow-up.     

药物洗脱支架对糖尿病血运重建中期临床结果的影响

目的评价药物洗脱支架(DES)对糖尿病患者冠状动脉血运重建结果的影响。方法回顾置入DES糖尿病患者的临床、冠状动脉病变与血运重建资料,并进行临床随访。结果204例糖尿病患者接受经皮冠状动脉介入治疗(PCI)时置入了一个或以上的DES,共置入316枚支架,其中DES254枚。180例患者术后接受了平均为9.3±5(6~26)个月的临床随访(随访率88.2%)。主要不良心脏事件(包括死亡、再梗死和再次血运重建)发生率为3.9%(8/204)。18例患者平均于PCI术后6.7(5.5~10)个月接受造影复查(造影随访率8.8%),经DES处理的病变无1例出现再狭窄。结论糖尿病患者使用DES安全有效,能显著降低再狭窄率和靶病变再次血运重建率。     

Cost-effectiveness of the unrestricted use of sirolimus-eluting stents vs. bare metal stents at 1 and 2-year follow-up: results from the RESEARCH Registry.

AIMS: To assess the cost-effectiveness of sirolimus-eluting stents (SESs) compared with bare metal stents (BMSs) as the default strategy in unselected patients treated in the Rapamycin Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry at 1 and 2-years following the procedure. METHODS AND RESULTS: A total of 508 consecutive patients with de novo lesions exclusively treated with SES were compared with 450 patients treated with BMS from the immediate preceding period. Resource use and costs of the index procedure, and clinical outcomes were prospectively recorded over a 2-year follow-up period. Follow-up costs were measured as unit costs per patient based on the incidence of clinically driven target vessel revascularization (TVR), to obtain cumulative costs at 1 and 2-years. Cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER) per TVR avoided. The use of SES cost euro 3,036 more per patient at the index procedure, driven by the price of SES. Follow-up costs after 1-year were euro 1,089 less with SES when compared with BMS, due to less TVR, resulting in a net excess cost of euro 1,968 per patient in the SES group, and reduced by a further euro 100 per patient in the second year. The incidence of death or myocardial infarction between groups was similar at 1 and 2 years. Rates of TVR in the SES and BMS groups were 3.7% vs. 10.4%, P<0.01 at 1 year, respectively; and 6.4% vs. 14.7%, P<0.001 at 2 years. The ICER per TVR avoided was euro 29,373 at 1 year, and euro 22,267 at 2 years. CONCLUSION: The use of SES, while significantly beneficial in reducing the need for repeat revascularization, was more expensive and not cost-effective in the RESEARCH registry at either 1 or 2-years when compared with BMS. On the basis of these results, in an unselected population with 1 year of follow-up, the unit price of SES would have to be euro 1,023 in order to be cost-neutral.     

伊贝沙坦洗脱支架预防动脉成形术后再狭窄量效关系

目的 探讨伊贝沙坦洗脱支架预防动脉成形术后再狭窄的量效关系。方法 把雄性新西兰白兔40只分为4组,裸支架组于腹主动脉植入裸金属支架,低剂量组植入200μg伊贝沙坦洗脱支架,中剂量组植入400μg伊贝沙坦洗脱支架,高剂量组植入600μg伊贝沙坦洗脱支架,均随访56日后取出支架作病理检查,测量血管腔面积、内膜面积、平均内膜厚度、狭窄程度。结果 裸支架组血管腔面积小于3个药物支架组（P＜0.05）,低剂量组小于中剂量组和高剂量组（P＜0.05）,中剂量组和高剂量组间无明显差异（P＞0.05）;裸支架组内膜面积、内膜厚度、狭窄程度高于药物支架组（P＜0.05）;而低剂量组高于中剂量组和高剂量组（P＜0.05）,中剂量组和高剂量组之间无明显差异（P＞0.05）。结论 伊贝沙坦洗脱支架预防动脉成形术后再狭窄有量效关系。     

Meta-analysis of randomized trials on drug-eluting stents vs. bare-metal stents in patients with acute myocardial infarction.

AIMS: To compare the efficacy and safety of drug-eluting stents vs. bare-metal stents in patients with acute ST-segment elevation myocardial infarction. METHODS AND RESULTS: We performed a meta-analysis of eight randomized trials comparing drug-eluting stents (sirolimus-eluting or paclitaxel-eluting stents) with bare-metal stents in 2786 patients with acute ST-segment elevation myocardial infarction. All patients were followed up for a mean of 12.0-24.2 months. Individual data were available for seven trials with 2476 patients. The primary efficacy endpoint was the need for reintervention (target lesion revascularization). The primary safety endpoint was stent thrombosis. Other outcomes of interest were death and recurrent myocardial infarction. Drug-eluting stents significantly reduced the risk of reintervention, hazard ratio of 0.38 (95% CI, 0.29-0.50), P < 0.001. The overall risk of stent thrombosis: hazard ratio of 0.80 (95% CI, 0.46-1.39), P = 0.43; death: hazard ratio of 0.76 (95% CI, 0.53-1.10), P = 0.14; and recurrent myocardial infarction: hazard ratio of 0.72 (95% CI, 0.48-1.08, P = 0.11) was not significantly different for patients receiving drug-eluting stents vs. bare-metal stents. CONCLUSION: The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stents.