Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation

Context  Recent studies of drug-eluting intracoronary stents suggest that current antiplatelet regimens may not be sufficient to prevent late stent thrombosis. Objective  To assess the association between clopidogrel use and long-term clinical outcomes of patients receiving drug-eluting stents (DES) and bare-metal stents (BMS) for treatment of coronary artery disease. Design, Setting, and Patients  An observational study examining consecutive patients receiving intracoronary stents at Duke Heart Center, a tertiary care medical center in Durham, NC, between January 1, 2000, and July 31, 2005, with follow-up contact at 6, 12, and 24 months through September 7, 2006. Study population included 4666 patients undergoing initial percutaneous coronary intervention with BMS (n = 3165) or DES (n = 1501). Landmark analyses were performed among patients who were event-free (no death, myocardial infarction [MI], or revascularization) at 6- and 12-month follow-up. At these points, patients were divided into 4 groups based on stent type and self-reported clopidogrel use: DES with clopidogrel, DES without clopidogrel, BMS with clopidogrel, and BMS without clopidogrel. Main Outcome Measures  Death, nonfatal MI, and the composite of death or MI at 24-month follow-up. Results  Among patients with DES who were event-free at 6 months (637 with and 579 without clopidogrel), clopidogrel use was a significant predictor of lower adjusted rates of death (2.0% with vs 5.3% without; difference, –3.3%; 95% CI, –6.3% to –0.3%; P = .03) and death or MI (3.1% vs 7.2%; difference, –4.1%; 95% CI, –7.6% to –0.6%; P = .02) at 24 months. However, among patients with BMS (417 with and 1976 without clopidogrel), there were no differences in death (3.7% vs 4.5%; difference, –0.7%; 95% CI, –2.9% to 1.4%; P = .50) and death or MI (5.5% vs 6.0%; difference, –0.5%; 95% CI, –3.2% to 2.2%; P = .70). Among patients with DES who were event-free at 12 months (252 with and 276 without clopidogrel), clopidogrel use continued to predict lower rates of death (0% vs 3.5%; difference, –3.5%; 95% CI, –5.9% to –1.1%; P = .004) and death or MI (0% vs 4.5%; difference, –4.5%; 95% CI, –7.1% to –1.9%; P<.001) at 24 months. However, among patients with BMS (346 with and 1644 without clopidogrel), there continued to be no differences in death (3.3% vs 2.7%; difference, 0.6%; 95% CI, –1.5% to 2.8%; P = .57) and death or MI (4.7% vs 3.6%; difference, 1.0%; 95% CI, –1.6% to 3.6%; P = .44). Conclusions  The extended use of clopidogrel in patients with DES may be associated with a reduced risk for death and death or MI. However, the appropriate duration for clopidogrel administration can only be determined within the context of a large-scale randomized clinical trial.      

药物洗脱支架置入后长期临床预后与氯吡格雷应用的关系

背景：近来关于冠状动脉内药物洗脱支架（DES）的研究表明目前的抗血小板方案不足以预防晚期支架内血栓形成。目的：评估冠心病患者接受DES和裸金属支架（BMS）置入后长期临床预后与氯吡格雷应用的关系。设计、地点和患者：对2000年1月1日至2005年7月31日间在Duke心脏中心接受冠状动脉支架置入术的连续患者进行观察研究。分别在6个月、12个月、24个月时进行随访，直至2006年9月7日。研究对象为4666例接受首次PCI支架置入的患者，其中3165例接受BMS，1501例接受DES。[第一段]     

The prevention and treatment of restenosis in the era of drug-eluting stent

Ever since the first percutaneous transluminal coronary angioplasty （PTCA） was completed successfully by Gruentzig in 1977, postoperational restenosis （RS） has been puzzling constantly the progress of percutaneous coronary intervention （PCI）, and it is known as the Achilles Heel of PCI. In a certain sense, the development history of PCI is also the history of continually overcoming RS.     

Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents

Context  Clinical trials that have excluded patients at high risk for cardiac events have led to commercial labeling approval of drug-eluting stents; nevertheless, such high-risk patients commonly undergo stent placement in clinical practice. The degree to which they experience cardiac events at a higher rate than non–high-risk patients is unclear. Objective  To assess the rates of major adverse cardiac events during the index admission and 1 year after the implantation of drug-eluting stents in patients with high-risk angiographic and clinical features. Design, Setting, and Patients  From July 2004 to September 2005, consecutive patients who underwent attempted stent placement at 42 different hospitals throughout the United States were enrolled in a prospective multicenter registry. We analyzed outcomes of 3323 patients who received at least 1 drug-eluting stent for a reason other than acute ST-segment elevation myocardial infarction. The study population was divided into 2 groups based on presence of at least 1 of 9 off-label characteristics based on the current US Food and Drug Administration–approved indications for sirolimus- and paclitaxel-eluting stents. Main Outcome Measures  The composite clinical outcomes of death, myocardial infarction, or target vessel revascularization during the index admission and death, myocardial infarction, or target lesion revascularization at 1 year were evaluated. Results  Of the 3323 patients, 1817 (54.7%) had at least 1 off-label characteristic. During the index hospitalization, the composite clinical outcome occurred in 198 (10.9%) of patients in the off-label group and 76 (5.0%) of patients in the on-label group (adjusted odds ratio, 2.32; 95% confidence interval [CI], 1.75-3.07; P<.001). At 1 year, the composite clinical outcome occurred more often in the off-label group compared with the on-label group; 309 (17.5%) vs 131 (8.9%) (adjusted hazard ratio [HR], 2.16; 95% CI, 1.74-2.67; P<.001). Stent thrombosis also occurred more frequently among patients in the off-label group during the initial hospitalization (8 [0.4%] vs 0) and at 1 year: 29 (1.6%) vs 13 (0.9%), adjusted HR, 2.29 (95% CI, 1.02-5.16; P = .05). Conclusions  Compared with on-label use, off-label use of drug-eluting stents is associated with a higher rate of adverse outcomes during the index admission and at 1 year. Stent thrombosis occurred predominantly in patients who underwent off-label drug-eluting stent implantation. Clinicians should be cautious about extrapolating the benefits of drug-eluting stents over bare-metal stents observed in randomized clinical trials to higher-risk clinical settings that have not been assessed.      

药物支架时代仍需关注临床因素对患者预后的影响

近年来,药物洗脱支架(drug-eluting stent,DES)的应用使经皮冠状动脉介入治疗(percutaneouscoronary intervention,PCI)术后再狭窄率显著降低.但影响患者介入术后近期和远期预后的因素不仅仅是冠状动脉本身的病变特点、采取的技术策略和支架类型,伴随的临床情况和动脉硬化相关危险因素也与支架术后再狭窄和动脉硬化的进展有着不可忽视的关系.因此,在DES广泛应用的今天,冠心病介入医师在制定治疗决策和评估预后时不应只关注病变,还应更多地关注患者.     

药物洗脱支架在预防支架内再狭窄中的作用及临床应用进展

冠状动脉支架植入术已成为冠心病治疗中一种有确切疗效的重要手段,但相当高(10％-50％)的支架内再狭窄率限制了支架植入术的发展。而可在局部缓慢释放抑制血管内皮和平滑肌增殖药物的药物洗脱支架(DES)的应用,明显降低了支架内再狭窄率,大大延缓了支架术后再次行经皮冠状动脉介入治疗的时间。目前临床应用的DES有雷帕霉素洗脱支架和紫杉醇洗脱支架。其显著降低支架内再狭窄率的作用已为越来越多的已完成或正在进行的临床试验所证实。     

PARTNER^TM药物洗脱支架的临床应用

目的：评价PARTNERTM药物洗脱支架的临床疗效及安全性。方法：选择2006年1～12月111例冠心病患者,所有患者行经皮冠状动脉介入治疗置入PARTNERTM药物洗脱支架,术后对患者进行随访,观察有无胸痛复发、心电图改变及重要心血管不良事件的发生。结果：111例患者共180处病变置入196枚PARTNERTM药物洗脱支架,手术成功率100%,胸痛缓解无复发,术后无重要心血管不良事件发生。结论：PCI术中应用国产PARTNERTM雷帕霉素药物洗脱支架近期疗效满意,应用安全方便。     

Comparison of home-made Firebird 2TM drug-eluting stent and imported Endeavor-Sprint drug-eluting stent

目的 对比研究国产Firebird 2TM雷帕霉素药物洗脱钴基合金支架与进口Endeavor-Sprint药物洗脱支架临床应用的安全性及疗效.方法 对100例冠心病患者进行介入治疗,随机分为Firebird组和Endeavor组,每组50例,比较两组支架植入后效果.结果 两组患者血管病变单支、双支、三支、分叉、慢性闭塞、左主干数比较差异无统计学意义(P>0.05),平均血管直径和平均靶病变长度比较差异无统计学意义(P>0.05);两组手术成功率为100%.Firebird组无血栓形成事件发生,Endeavor组发生1例亚急性血栓形成事件,且进行血运重建.Firebird组28例复查冠状动脉造影,1例再狭窄;Endeavor组19例复查冠状动脉造影,2例有再狭窄,两组比较差异无统计学意义(P>0.05).结论 Firebird 2TM雷帕霉素药物洗脱钴基合金支架具有良好的安全性和满意的近、中期疗效.其与进口Endeavor-Sprint药物洗脱支架比较无明显差别.     

Long-term outcomes following drug-eluting stent implantation in unprotected left main bifurcation lesions

Background The safety and efficacy of drug-eluting stents （DES） implantation in unprotected left main （LM） bifurcation lesions has yet to be determined. The aim of the present report was to evaluate the long-term outcome following implantation of DES in unprotected LM bifurcation lesions. Methods We identified 70 consecutive patients treated with DES in unprotected LM bifurcation lesions from April 2003 to January 2005. Of them, 42 patients were treated with sirolimus-eluting stent （SES） and 28 patients were treated with paclitaxel-eluting stent （PES）. Results Stents to the left anterior descending and to the circumflex were implanted in 62 patients. During 1-year follow-up, 3 （4.3%） patients died of cardiac causes. One of them had myocardial infarction and adjudicated as possibly due to stent thrombosis. Angiographic follow-up was available in 80% of patients. The per lesion restenosis rate was 13.4% in the entire cohort, of which 10.7% occurred in lesions treated with SES and 16.1% in those treated with PES （P=0.58）. All restenosis was focal and occurred in the lesions treated with a stent with stent size to post-procedural reference vessel diameter ratio 〈1.0 （17.6% vs 0, P=0.04）. The per patient target lesion revascularization rate at 1 year was 17.1%. One year survival free from major adverse cardiac events was 77.1%. Conclusions Treatment of LM bifurcation lesions using DES is a safe and feasible way with a low one-year mortality. The need for revascularization in 17% of patients demands for improvement.     

Two-year clinical outcomes following elective drug-eluting versus bare-metal stent implantation: results from a large single-center database

Background In response to the increasing concern with the safety of the drug-eluting stent （DES）, the present study aimed to evaluate the long-term safety and efficacy of DES used for a Chinese patient population. Methods All patients, who underwent an index elective percutaneous coronary intervention with an implantation of either DES or bare-metal stent （BMS） in a single institution from April 2004 to December 2006, were included in the analysis. A propensity-score matching technique was applied to adjust and to minimize the impact of confounding factors. Results Overall, there were 1465 patients （20.2%） who had undergone an implantation of only BMS, and 5769 patients （79.8%） of only DES. The propensity-score matching technique set up 1321 pairs of patients for analysis. There were no significant differences between the rates of stent thrombosis （definite and probable） of the two groups （1.06% vs 1.21%, P=0.8580）. Although rates of mortality and myocardial infarction （MI） during the 2-year follow-up period had not differed significantly, rates of death/MI （3.0% vs 4.5%, P=0.0263）, target-lesion revascularization （TLR, 3.2% vs 8.5, P=0.0001）, target-vessel revascularization （TVR, 5.8% vs 9.5%, P 〈0.0001） and any revascularization （10.0% vs 13.3%, P=0.0066） were significantly lower for the DES group than for the BMS group. Among the patients in whom devices were implanted for off-label indications, the propensity-score matched rates of stent thrombosis, mortality, MI, and death/MI were not significantly different, while rates of TLR, TVR and any revascularization were significantly lower for the DES group than for the BMS group. Conclusions During the 2 years of follow-up post stenting, DES use is associated with lower rates of death/MI, TLR, TVR and any revascularization, compared with BMS, in propensity-score matched Chinese patient populations. In the setting of off-label usage, DES use is also associated with similar advantages.     

Vascular brachytherapy revisited for in-stent restenosis in the drug-eluting stent era: current status and future perspective

Percutaneous coronary intervention （PCI） with drug-eluting stents （DESs） has revolutionized the management of atherosclerotic coronary artery disease. However, in-stent restenosis （ISR） has been the downside of all coronary interventions with the devices that have been tested so far, even in the DES era. The impact of ISR is still an important issue due to the recurrent costs from need for repeat PCI and bypass surgery in some patients who underwent PCI with DES. A safe and cost-effective method is desired to overcome this unfavorable burden following PCI with DES. Vascular brachytherapy （VBT） is one of the approved indications and has evolved over a decade as a valuable alternative to treat ISR. Although VBT has been regarded as a standard therapy in ISR, it has cumbersome logistics and global applicability is decreasing, leading more extensive introduction of DES.     

国产Firebird 2TM与进口Endeavor-Sprint药物洗脱支架临床应用比较

目的对比研究国产Firebird 2TM雷帕霉素药物洗脱钴基合金支架与进口Endeavor-Sprint药物洗脱支架临床应用的安全性及疗效。方法对100例冠心病患者进行介入治疗,随机分为Firebird组和Endeavor组,每组50例,比较两组支架植入后效果。结果两组患者血管病变单支、双支、三支、分叉、慢性闭塞、左主干数比较差异无统计学意义(P>0.05),平均血管直径和平均靶病变长度比较差异无统计学意义(P>0.05);两组手术成功率为100%。Firebird组无血栓形成事件发生,Endeavor组发生1例亚急性血栓形成事件,且进行血运重建。Firebird组28例复查冠状动脉造影,1例再狭窄;Endeavor组19例复查冠状动脉造影,2例有再狭窄,两组比较差异无统计学意义(P>0.05)。结论 Firebird 2TM雷帕霉素药物洗脱钴基合金支架具有良好的安全性和满意的近、中期疗效。其与进口Endeavor-Sprint药物洗脱支架比较无明显差别。     

光学相干断层成像评价药物洗脱支架与金属裸支架治疗后的内膜增殖

目的应用光学相干断层成像(OCT)技术比较冠状动脉内雷帕霉素药物洗脱支架(DES)和金属裸支架(BMS)治疗后内膜增殖情况。方法对19例冠心病经冠状动脉内支架置入治疗后5~93个月的患者进行冠状动脉造影复查,造影后对21支血管23个支架进行OCT成像检查。DES术后6~10个月为药物支架A组;BMS术后5~10个月为金属裸支架B组;BMS术后23~93个月为金属裸支架C组。应用OCT成像技术比较3组支架之间内膜增殖情况。结果OCT成像结果显示3组之间有关支架后最大内膜增殖厚度、血管腔直径和截面积丢失及直径和截面积再狭窄等方面差异有统计学意义。其中A组内膜最大增殖厚度明显小于B组(0·20mm±0·13mmvs0·81mm±0·46mm,P=0·019)和C组(0·91mm±0·27mm,P=0·007);A组血管腔直径丢失明显小于B组(0·27mm±0·17mmvs1·12mm±0·79mm,P=0·009)和C组(1·20mm±0·31mmP=0·013);A组直径再狭窄明显小于B组(8%±4%vs36%±24%,P=0·009)和C组(35%±6%,P=0·017);A组截面积丢失明显小于B组(1·14mm2±0·9mm2vs3·96mm2±2·62mm,P=0·009)和C组(4·66mm2±1·66mm2,P=0·006);A组截面积再狭窄明显小于B组(P=0·017)和C组(P=0·009)。置入的13个BMS支架,几乎所有支架支撑杆表面均有内膜覆盖,而置入DES后内膜增殖较少,部分支架支撑杆表面即使在支架术后29个月仍然没有内膜覆盖。结论OCT成像技术可清晰地显示支架支撑杆及表面内膜增殖情况,对评价药物洗脱支架的治疗效果具有重要意义。     

A high maintenance dose of clopidogrel improves short-term clinical outcomes in patients with acute coronary syndrome undergoing drug-eluting stent implantation

Background Recurrent ischemic events occurred even during routine use of 75 mg clopidogrel in addition to aspirin, that indicated a potentially insufficient maintenance dosage of clopidogrel. The aim of the present study was to evaluate the short-term efficacy and safety of a 150 mg maintenance dose of clopidogrel following a 600 mg loading dose in patients with an acute coronary syndrome （ACS） undergoing drug eluting stent （DES） implantation.
Methods Between November 2005 and November 2006, a total of 813 consecutive ACS patients undergoing DES implantation were enrolled. A 600 mg loading dose was administered before percutaneous coronary intervention （PCI） and patients were randomized to receive clopidogrel 75 mg or 150 mg for 30 days in addition to 300 mg aspirin daily. Primary end points were the composite of cardiac death, non-fatal myocardial infarction （MI） and urgent target vessel revascularization （UTVR）. Secondary end points included stent thrombosis （ST）, major and minor bleeding events at 30 days. Results At a follow-up period of 30 days, 4 （1.0%） patients in the 150 mg group and 9 （2.2%） patients in the 75 mg group （P 〉0.05） reached the primary end points. There was no significant difference in the incidences of MI （0.5% vs 1.2%, P〉0.05）, UTVR （0.7% vs 2.0%, P 〉0.05）, and cardiac death （0.2% vs 0.2%, P 〉0.05） between the two groups. The incidence of ST （0 vs 1.5%, P 〈0.05） was significantly lower in the 150 mg group than that in the 75 mg group. There were no significant differences between both groups regarding the risk of major （0.2% vs 0, P 〉0.05） or minor （0.5% vs 0.2%, P 〉0.05） bleedings.
Conclusion A high clopidogrel maintenance dose of 150 mg daily following a 600 mg loading dose for the first month after PCI procedure reduces the risk of ST and appears to be safe in patients with ACS undergoing DES implantation.     

Comparison of drug-eluting stent and bare-mental stent in the complex small vessel intervention

Nowadays, coronary intervention has been dramatically improved in the drug-eluting stent era. The drug-eluting stent represents the dominant percutaneous coronary intervention modality beacause it significantly reduces the restenosis rate compared with bare mental stent. Such benefit was initially demonstrated in coronary vessels 3 mm or more in diameter.1,2 However, restenosis after coronary stent implantation is influenced by vessel size and length, and stent occlusion is more frequent in sm…     

PARTNER~(TM)药物洗脱支架的临床应用

目的:评价PARTNERTM药物洗脱支架的临床疗效及安全性。方法:选择2006年1～12月111例冠心病患者,所有患者行经皮冠状动脉介入治疗置入PARTNERTM药物洗脱支架,术后对患者进行随访,观察有无胸痛复发、心电图改变及重要心血管不良事件的发生。结果:111例患者共180处病变置入196枚PARTNERTM药物洗脱支架,手术成功率100%,胸痛缓解无复发,术后无重要心血管不良事件发生。结论:PCI术中应用国产PARTNERTM雷帕霉素药物洗脱支架近期疗效满意,应用安全方便。