Sirolimus PK trial: a pharmacokinetic study of the sirolimus-eluting Bx velocity stent in patients with de novo coronary lesions.

This study was conducted to assess the systemic drug release and distribution of sirolimus-eluting stents. Early results with sirolimus-eluting stents have demonstrated a favorable outcome for reducing restenosis post coronary intervention. However, the clinical systemic pharmacokinetics of sirolimus released from these stents has not been investigated. Sirolimus-eluting stents (150-178 mcg/18 mm stent) were implanted in 19 patients with coronary artery disease using standard techniques. Blood samples were obtained at multiple times to determine the kinetics of sirolimus release and elimination. Non-compartmental analysis showed that the maximum blood concentration of sirolimus occurred between 3 and 4 hr after implantation, with a peak concentration of 0.57 +/- 0.12 ng/mL (mean +/- SD) and 1.05 +/- 0.39 ng/mL in patients receiving one or two stents, respectively. Terminal-phase elimination half-life was independent of the number of stents and averaged at 213 hr, a value longer than that seen in patients following oral dosing. The apparent clearance was 1.46 +/- 0.45 L/hr with an apparent volume of distribution in the terminal phase of 407 +/- 111 L (data for both stent doses pooled). Minimal measurable blood levels were detectable at 7 days. Peak whole blood level following sirolimus stent implantation in humans is proportional to the number of stents implanted. The prolonged terminal half-life may reflect kinetics of blood clearance combined with continued drug elution and secondary local tissue release.     

The SIRIUS-DIRECT trial: a multi-center study of direct stenting using the sirolimus-eluting stent in patients with de novo native coronary artery lesions.

OBJECTIVE: To assess the safety and efficacy of direct stenting using the sirolimus-eluting BX Velocitytrade mark stent in patients with coronary lesions. BACKGROUND: Although direct coronary stenting has become a widespread practice, there have been no systematic assessments of direct stenting with drug-eluting stents. METHODS: Total of 225 patients with identical inclusion and exclusion criteria as the original SIRIUS trial were enrolled in this prospective single-arm study. They were compared in a no-inferiority design with 412 similar patients from the SIRIUS trial who had sirolimus-eluting stents deployed after predilatation and were preassigned to angiographic follow-up evaluation. RESULTS: Direct stenting was successful in 85.8% of the patients. Compared with the predilatation group, direct stenting was associated with shorter median procedure duration (33 min vs. 45 min, P < 0.001). Angiographic follow-up at 8 months revealed similar late loss (in-stent-0.19 +/- 0.47 mm vs. 0.17 +/- 0.44 mm, and in-lesion-0.23 +/- 0.41 mm vs. 0.24 +/- 0.47 mm) and similar frequency of binary restenosis (in-stent-4.6% vs. 3.2% and in-lesion-6.1% vs. 8.9%) between the two treatment strategies. However, stent-edge restenosis was lower with direct stenting than in the predilatation control group (2.1% vs. 6.9%, P = 0.02). At 12-months, there were no significant differences in target lesion revascularization (3.7% vs. 5.1%, P = ns) or composite major adverse cardiac events (7.0% vs. 8.3%, P = ns). CONCLUSIONS: In patients similar to those treated in the SIRIUS trial, direct stenting using sirolimus-eluting stents achieves excellent short- and long-term clinical and angiographic results with shorter procedure time and less frequent stent edge restenosis compared with predilation stent implantation techniques.     

雷帕霉素药物洗脱支架治疗冠状动脉小血管病变的临床即刻效果

目的评价国产雷帕霉素药物洗脱支架(Firebird支架)治疗冠状动脉小血管病变(直径≤2.5mm)的临床即刻效果。方法采用前瞻性、非随机对比研究方法,根据入选和剔除标准,连续入选2004年6月~2007年2月我院行冠状动脉造影(CAG)确诊,首次接受经皮冠状动脉介入治疗(PCI)的靶血管为小血管病变且达到完全血运重建的160例患者,根据所置入的支架分为Firebird组(82例)和Cypher组(78例);支架置入后以相同的方法进行CAG,观察对比反映临床即刻效果的相关参数。结果术中全部Cypher及Firebird支架均顺利到达并释放于靶病变部位。两组支架的PCI手术成功率均为100%。Firebird组病变部位狭窄程度由术前的(78.7±15.6)%减至(7.20±10.69)%,P=0.0005;而Cypher组病变部位狭窄程度由术前的(79.8±15.8)%减至(7.10±10.61)%,P=0.0004。在急性管腔直径获得方面,Firebird组(1.76±0.52)mm与Cypher组(1.77±0.53)mm之间无显著差异(P=0.46)。结论Cypher和Firebird支架治疗冠状动脉小血管病变安全可行,临床即刻效果好。     

雷帕霉素洗脱支架治疗冠状动脉特长病变的临床研究

目的研究雷帕霉素洗脱支架(SES)治疗冠状动脉(冠脉)特长病变的疗效。方法对41例冠脉特长病变患者置入SES并对其进行随访,于6个月时行冠脉造影检查。结果41例患者完成该研究,共45处病变。病变长度平均(52.60±15.40)mm,直径平均(2.74±0.10)mm,每处病变平均置入2.5枚支架。6个月造影随访显示,支架近端狭窄由13%上升到15%,支架内狭窄由15%上升到22%,支架远端狭窄由25%下降到20%。6个月内的主要心脏事件有1例非致死性心肌梗死和2例心绞痛,无死亡。结论SES治疗冠脉特长病变是安全可靠的,效果优于金属裸支架。     

药物洗脱支架与冠状动脉旁路移植术治疗冠状动脉多支病变的比较

目的比较药物洗脱支架与冠状动脉旁路移植术治疗冠状动脉复杂多支病变的疗效。方法连续入选行血运重建治疗的冠心病多支病变患者200名,随机分为经皮冠状动脉介入(PCI)组和冠状动脉旁路移植术(CABG)组,每组100例。PCI组和CABG组中分别有合并糖尿病者(糖尿病亚组)27例和25例。观察术后1年内主要心脑血管不良事件(死亡、脑卒中、非致死性心肌梗死、靶血管再次血运重建)、再狭窄、心绞痛复发发生率,血浆肌酸激酶水平和PCI组支架内血栓形成发生率。结果两组患者的基线特征差异无统计学意义。PCI组与CABG组1个月、6个月和1年的主要心脑血管不良事件发生率分别为4.0%、7.0%、12.0%比6.0%、9.0%、15.2%(P>0.05);心绞痛复发率分别为2.0%、4.0%、6.0%比1.0%、3.0%、5.1%(P>0.05)。术后1年再狭窄率分别为11.3%比13.2%(P>0.05)。PCI组术后亚急性血栓形成率1.0%。PCI组和CABG组术后肌酸激酶MB型同工酶升高的患者比例分别为26%比82%(P<0.05)。PCI组糖尿病亚组与CABG组糖尿病亚组1个月、6个月和1年的严重心脑血管不良事件发生率分别为7.4%、11.1%、18.5%比8.0%、16.0%、24.0%(P>0.05)。结论药物洗脱支架时代PCI与CABG治疗冠状动脉多支病变的近、远期疗效相近,对于合并糖尿病的患者同样有效。     

国人应用雷帕霉素药物洗脱支架预防再狭窄的初步经验--Sino-SIRIUS临床试验

目的　研究雷帕霉素药物洗脱支架对国人自身冠状动脉第一次进行介入治疗的病变减少再狭窄的效果及安全性。方法　本试验为在 2个中心进行的开放、前瞻性研究。入选标准包括对单一病变 (2 5mm≤靶病变直径≤ 3 0mm)进行治疗 ,长度≤ 30mm ,至少TIMI 1级血流。排除标准包括无保护的左主干病变、开口部病变、左室射血分数≤ 2 5 %、完全闭塞病变 (TIMI 0级 )以及分叉病变侧支直径≥ 2 5mm者。术后 1、3和 6个月进行临床随访 ,术后 6个月造影随访 ,核心试验室 (纽约心血管研究基金会 )进行QCA分析。结果　 4 1例患者入选本研究 ,其中男性 30例 (占 73 2 % ) ,平均年龄 (5 8 6± 11 0 )岁 ,合并糖尿病患者 12例 (占 2 9 3% )。基础冠状动脉造影示参考血管直径(2 5 8± 0 35 )mm ,最小管腔直径 (MLD) (0 77± 0 33)mm ,直径狭窄 (DS % )为 (6 9 77± 12 16 ) % ,病变长度 (14 2 7± 3 72 )mm。支架置入后 ,MLD支架内 (2 4 4± 0 2 8)mm ,节段内 (2 15± 0 38)mm ;DS %支架内 (8 5 8± 9 18) % ,节段内 (19 92± 9 99) %。 6个月造影随访 ,MLD支架内 (2 4 7±0 32 )mm ,节段内 (2 0 6± 0 38)mm ;DS %支架内 (6 6 9± 10 5 3) % ,节段内 (2 2 5 9± 10 2 1) % ;晚期管腔丧失支架内为 ( 0     

The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS)

OBJECTIVES: We assessed the safety and effectiveness of the sirolimus-eluting stent (SES) in treating single de novo long lesions in small native coronary arteries compared to an identical bare metal stent (BMS). BACKGROUND: The SES was previously demonstrated to reduce restenosis significantly. However, patients with long lesions in small vessels have not been well studied and may define a group at very high risk. METHODS: The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients With Long De Novo Lesions in Small Native Coronary Arteries (C-SIRIUS) was a multicenter, randomized, double-blind trial comparing SES versus identical BMS. The primary end point was in-stent minimal lumen diameter (MLD) at eight months. Secondary end points included angiographic restenosis at 8 months, target lesion revascularization (TLR), and major adverse cardiac events (MACE) at 270 days. RESULTS: A total of 100 patients were enrolled at eight Canadian sites. The in-stent MLD at eight months was 2.46 +/- 0.37 mm in the SES compared with 1.49 +/- 0.75 mm in the BMS (a 65% increase, p < 0.001). Angiographic restenosis occurred in 1 of 44 SES patients (2.3%, with no in-stent restenosis) and in 23 of 44 BMS patients (52.3%, p < 0.001). At 270 days, there were two clinically driven TLRs in the SES (4%) and nine in the BMS (18%, p = 0.05). The Kaplan-Meier estimate of freedom from MACE at 270 days was 96.0% for SES patients and 81.7% for BMS patients (p = 0.029). CONCLUSIONS: Patients with long lesions in small vessels are at very high risk of restenosis. In these patients, the SES dramatically reduces the risk of restenosis at eight months, translating into an excellent clinical outcome at nine months.     

Direct stenting of native de novo coronary artery lesions with the sirolimus-eluting stent: a post hoc subanalysis of the pooled E- and C-SIRIUS trials

OBJECTIVES: We sought to assess the impact of direct stenting (DS) using the sirolimus-eluting stent (SES) on angiographic and clinical outcomes. BACKGROUND: The SES is superior to bare-metal stents in the treatment of native de novo coronary artery lesions in randomized, controlled trials. METHODS: A post hoc analysis was performed on 225 patients (158 men; 62 +/- 11 years old) who received SES in the pooled cohorts of the European and Canadian Sirolimus-Eluting Stent in Coronary Lesions (E-SIRIUS and C-SIRIUS, respectively) trials. Of these patients, 57 (25%) had undergone DS at the investigator's discretion. Lesion predilation preceded SES implantation in the remaining 168 patients. RESULTS: Patient and lesion characteristics were no different between the two subgroups, except for a lower prevalence of moderate to severe lesion calcification (5% vs. predilation 19%, p=0.017) and a lower baseline diameter stenosis (61.6% vs. predilation 68.1%, p <0.001) in the DS subgroup. At eight months, in-lesion late loss (0.10 vs. 0.19 mm at predilation, p=0.14) and in-lesion binary restenosis (2.0% vs. 6.1% at predilation, p=0.46) tended to be lower after DS. Clinical follow-up at one year revealed non-significantly reduced incidences of target lesion revascularization (1.8% vs. 5.4% at predilation, p=0.46) and major adverse cardiac events (5.3% vs. 8.9% at predilation, p=0.57). CONCLUSIONS: Direct SES deployment performed at the investigator's discretion was as safe and efficacious at mid-term follow-up as stenting preceded by lesion predilation.     

ISR II study: a long-term evaluation of sirolimus-eluting stent in the treatment of patients with in-stent restenotic native coronary artery lesions.

The aim of this pilot study was to determine the safety and long-term efficacy of treating intrastent restenosis (ISR) with the slow-release sirolimus-eluting stent Bx Velocity (Cypher stent) without intravascular ultrasound (IVUS) guidance. Of patients who received a bare metal stent implantation and presented an ISR, 30-80% of the patients will develop a second restenosis within the stent, at the stent edges or both. To date, intravascular brachytherapy using beta- and gamma-radiation has been the only effective treatment for ISR. Twenty-three patients with ISR and evidence of ischemia were treated with Cypher stent. Clinical information was collected 1, 8, 12, and 24 months after stent implantation. During the first 8 months of the study, in-stent lumen diameter remained essentially unchanged from postprocedure in 80% of the case. The target lesion repeat revascularization (TLR) was 17%, of which 50% were oculostenotic reflexes. Only one patient presented a restenosis greater than 70%. During the 2-year study period, the TLR rate was 17%; the major adverse coronary event rate was 26%, and the non-Q-wave myocardial infarction (MI) rate was 9%. There were no reports of death, coronary artery bypass grafting, or Q-wave MI during the study. This study demonstrates the feasibility of using sirolimus-eluting stents without IVUS guidance for the treatment of ISR, providing long-term stability of immediate results.     

Long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases

正Objective To evaluate the long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases.Methods CREDITⅡtrial was a prospective,multicenter,randomized,controlled study,conducted at 15 Chinese cardiac centres from November     

Prospective registry evaluating safety and efficacy of cobalt-chromium stent implantation in patients with de novo coronary lesions

BACKGROUND: Cobalt-chromium (Co-Cr) stents are a new type of endovascular prostheses characterised by better mechanical properties than traditional stainless steel stents. AIM: To assess the safety and efficacy of percutaneous coronary interventions (PCI) using the new Co-Cr Kos stent (Balton, Poland). METHODS: A total of 59 patients with coronary artery diseases (76% men, aged 60+/-9 years, diabetes - 16.9%, smoking - 62.7%, 11.8% - acute myocardial infarction) underwent PCI for de novo lesions in native coronary vessels. The patients were followed for 6 months for the occurrence of cardiac events. Quantitative coronary angiography was performed at baseline and after 6 months. RESULTS: In total, we implanted 62 stents in 59 coronary arteries. The mean diameter of the stents was 3.18+/-0.18 mm, and length - 14.62+/-2.12 mm. During a one-month follow-up period no cardiac events were noted. During a 6-month follow-up no death or new myocardial infarction were recorded. Control angiography was done in 55 (92%) subjects. Repeated target vessel revascularisation due to recurrent angina or in-stent restenosis was required in 10 (17%) patients; however, off-line core evaluation found significant re-narrowing in implanted stents (>50% diameter stenosis) only in 6 cases (10.9%). The mean late vessel lumen loss was 0.55+/-0.6 mm and stenosis 25.2+/-17.9%. CONCLUSIONS: Implantation of the new Co-Cr Kos stent during PCI is safe and effective.