氯吡格雷应用冠心病患者药物洗脱支架术后疗效观察

目的:探讨不同剂量的氯吡格雷对冠心病药物洗脱支架术后患者的疗效。方法:选取接受药物洗脱支架置入术的77例患者,随机分为两组,高剂量组予以术后150mg/d氯吡格雷口服,低剂量组予以术后75mg/d口服维持治疗。随访1年,比较两组患者心血管事件及出血并发症的发生情况。结果:两组患者在随访一年期间,急性心肌梗死、脑梗死和心源性梗死的发生率差异无统计学意义(P>0.05)。但低剂量组的心绞痛再发率较高剂量组有所增加,差异存在统计学意义(P<0.05)。低剂量组心血管事件总发生率为47.37%,明显高于高剂量组的17.95%(P<0.05)。低剂量组患者发生3例轻度和1例中度出血并发症;而高剂量组患者发生5例轻度和2例中度出血并发症,但差异均无统计学意义(P>0.05)。两组患者随访期间均无重度出血并发症发生。结论:采用高剂量(150mg/d)氯吡格雷作为药物洗脱支架术后的维持治疗,能够有效降低术后1年内的心血管事件发生风险,且不增加出血风险,具有较好的疗效及安全性。     

氯吡格雷的使用与药物洗脱支架植入后远期临床结果

背景：近来的冠状动脉内药物洗脱支架研究提示，现行的抗血小板治疗方案可能并不足以预防后期支架内血栓形成。目的：于接受药物洗脱支架（drug-eluting stents，DESs）和裸金属支架（bare-metal stents，BMSs）治疗的冠状动脉病患者中评估氯吡格雷使用与患者远期结果的关系。设计、地点及患者：于连续患者中进行观察性研究。患者于2000年1月1日至2005年7月31日在杜克心脏治疗中心（一家位于北卡罗来纳州达累姆市的三级治疗中心）接受冠状动脉内支架治疗。于6、12、24个月时进行随访，直至2006年9月7日。研究人群包括4666例最初接受BMS（n=3165）或DES（n=1501）经皮冠状动脉介入治疗的患者。对随访6和12个月没有事件（没有死亡、心肌梗死或血管重建手术）的患者进行界标分析（landmark analysis）。在这些时间点上根据支架类型以及自我报告之氯吡格雷的使用情况将患者分为4组：DES使用氯吡格雷组、DES不用氯吡格雷组、BMS使用氯吡格雷组以及BMS不用氯吡格雷组。主要观测指标：随访24个月时死亡、非致命性心肌梗死以及死亡或心肌梗死之复合终点。结果：在6个月时没有事件发生的DES组患者（637例使用、579例未使用氯吡格雷）中，氯吡格雷的使用是随访24个月校正死亡率较低（使用2．0％比未使用5．3％；差异，-3．3％；95％CI，-6．3％至-0．3％；P=0．03）以及死亡或心肌梗死发生率较低（3．1％比7．2％；差异，-4．1％；95％CI，-7．6％至-0．6％；P=0．02）的显著预测指标。然而，在BMS组患者中（417例使用、1976例未用氯吡格雷），死亡（3．7％比4．5％；差异，-0．7％；95％CI，-2．9％至1．4％；P=0．50）以及死亡或心肌梗死发生率（5．5％比6．0％；差异，-0．5％；95％CI，-3．2％至2．2％；P：0．70）没有差异。在12个月随访没有事件发生的DES组患者（252例使用、276例未用氯吡格雷）中，氯吡格雷的使用依然可以预测24个月死亡（0％比3．5％；差异，-3．5％；95％CI，-5．9％至-1．1％；P=0．004）以及死亡或心肌梗死发生率（0％比4．5％；差异，-4．5％；95％CI，-7．1％至-1．9％；P〈0．001）较低。然而，在BMS组患者中（346例使用、1644例未用氯吡格雷），在死亡（3．3％比2．7％；差异，0．6％；95％CI，1．5％至2．8％；P=0．57）以及死亡或心肌梗死（4．7％比3．6％；差异，1．0％；95％CI，-1．6％至3．6％；P=0．44）发生方面，依然没有差异。结论：在接受DES治疗的患者中，延长氯吡格雷的使用可以使死亡以及死亡或心肌梗死的发生率下降。然而，使用氯吡格雷的适宜期限只能通过大型临床随机试验确定。     

停用氯吡格雷后的晚期不良事件会降低植入药物洗脱支架患者的获益程度

药物洗脱支架（drug-eluting stent，DES）与金属裸支架（bare-metal stent,BMS）相比具有更好的疗效,主要体现在DES通过抑制内膜的过度增生使血管再狭窄率和靶病变血运重建率（target vessel revascularization，TVR）显著降低。而死亡和非致死性心肌梗死（myocardial infarction，MI）的发生率与BMS基本相同。     

药物洗脱支架介入治疗冠状动脉多支病变的临床研究

目的：观察全部置入药物洗脱支架（DES）对冠状动脉介入治疗（PCI）多支架术患者临床结果的影响。方法：选取2004年5月1日至2009年4月30日接受冠状动脉多支架术治疗的患者共913例。根据置入支架的种类不同分为3组,分别记录三组病人的临床基本情况、冠状动脉病变的基础特征、支架置入的部位和种类、病人住院期间治疗情况及主要的心脑血管事件发生情况和出院后中位数的随访情况等,对比观察全部置入DES对PCI多支架术患者临床结果的影响。结果：全部置入DES组中既往有血管重建史的患者明显增多。单支病变全部应用DES多,占31.9%,三支病变应用DES和混合组为多,占42.3%,3组在2支病变中支架应用无差异;在左主干病变、前降支近端病变、开口病变、弥漫性病变及支架内再狭窄病变中BMS组比例最少。住院期间心脑血管不良事件（MACCE）发生率三组患者均较低。结论：全部置入DES在PCI多支架术中的应用是安全、有效的。     

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]     

药物洗脱支架术后支架内亚急性血栓的发生和原因分析

目的分析冠状动脉药物洗脱支架（drug—eluting stent,DES）置入术后支架内亚急性血栓形成的因素及治疗措施。方法回顾性分析2004年12月至2008年4月我院心内科冠心病患者行药物洗脱支架置入术后11例患者发生支架内亚急性血栓的好发时间、部位及相关危险因素。结果2004年12月至2008年4月,我院共完成PCI术596例,其中DES置入术455例,术后发生支架内亚急性血栓11例,发生率为2．42％,血栓形成时间为3—15d,平均（6．9±4．1）d。其中冠脉3支病变患者5例,2支血管病变4例;左前降支病变6例;置入多支架8例;支架贴壁不良2例。支架置入术后突然出现无其他原因可以解释的明显胸痛者7例;心衰低血压状态2例;以心脏骤停发病者2例,均院外死亡。心电图提示支架段血管支配区域心肌缺血加重或急性心梗2例,造影复查证实原支架内闭塞伴血栓影像7例,术后突然出现无其他原因可以解释死亡2例。4例因停用氯吡格雷而致血栓形成;2例可能支架贴壁不良。经单纯球囊扩张,冠脉内注入血小板GPⅡb／Ⅲa受体拮抗剂等治疗,7例患者存活出院,4例患者死亡（病死率36．4％）。结论亚急性支架内血栓形成与患者临床病变特点、介入操作因素和支架本身、抗凝治疗等有关,多发生在AMI、合并糖尿病或心功能不全、多支血管病变、前降支病变、B／C型复杂病变等患者。急诊再次介入治疗是治疗支架内血栓的首选。     

药物洗脱支架内血栓形成的防治策略

药物洗脱支架(drug-eluting stent,DES)置入是继冠状动脉腔内成形术、裸金属支架(bare metal stent,BMS)置入之后经皮冠状动脉介入治疗(percutaneous coronary intervention,PCT)的第3个里程碑.雷帕霉素(Sirolimus)或紫杉醇(Paclitaxel)等涂层药物支架的再狭窄率在10%以下,比BMS的再狭窄率(15%～20%)明显降低[1],同时降低了靶血管的血运重建,在全球范围内迅速取代BMS而成为主要的冠脉介入手段.     

药物洗脱支架术后再狭窄的研究现状及进展

经皮冠状动脉介入治疗（PCI）已经成为冠心病治疗的一个重要手段,但术后再狭窄一直困扰着临床医生。药物洗脱支架（DES）较金属裸支架（BMS）在降低支架内再狭窄方面有显著疗效。以往大规模临床多中心随机双盲对照研究结果显示,对“罪犯”病变行冠状动脉内药物洗脱支架,术后支架内再狭窄已降至10％以下。但由于DES抗增殖药物延迟血管损伤反应过程,抑制平滑肌细胞增生同时也可能抑制内皮细胞愈合,进而导致再狭窄时间上的延迟及晚发血栓形成。     

采用药物洗脱支架植入术联合氯吡格雷治疗冠心病的临床体会

目的:探讨药物洗脱支架植入术联合氯吡格雷治疗冠心病的临床效果。方法:选取2010年8月至2012年10月西平县人民医院收治的98例冠心病患者,按照随机数字法分为观察组和治疗组,各49例。对照组给予药物洗脱支架植入术联合阿司匹林长期口服治疗,观察组给予药物洗脱支架植入术联合氯吡格雷长期口服治疗,对两组患者治疗效果进行对比分析。结果:观察组患者在心血管事件在发生率、再次住院率、晚期血栓发生率方面明显优于对照组,差异有统计学意义(P<0.05),但在死亡率方面,两组患者差异无统计学意义(P>0.05)。结论:药物洗脱支架植入术联合氯吡格雷治疗冠心病效果肯定,患者远期预后好,是理想的治疗手段。     

冠心病国产药物洗脱支架术后再狭窄的观察

目的观察国产药物洗脱支架植入术后1年及2年的支架内再狭窄情况。方法588例冠心痛患者均植入国产药物洗脱支架，分别于术后1年（279例）和2年（309例）复查冠状动脉造影，观察支架内再狭窄的发生率。结果国产药物洗脱支架植入后1年、2年冠脉支架内再狭窄率分别为4．66％、6．15％，两者差异无统计学意义（P〉0．05）。结论国产药物洗脱支架植入后支架内再狭窄发生率较低，支架植入术后1年、2年再狭窄率无明显差异。     

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

Context  Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. Objective  To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Design, Setting, and Patients  Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Interventions  Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Main Outcome Measures  Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. Results  At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). Conclusions  The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.      

Incidence of thrombosis after implantation of drug-eluting stents in patients with coronary artery disease

Background Randomized clinical trials have demonstrated equivalent safety to bare-metal stents after drug-eluting stents （DES） implantation. However, the DES thrombosis in randomized trials could not be comparable to those observed in clinical practice, frequently including off-label indications. This study sought to assess the incidence of DES thrombosis after implantation of DES in patients with real world coronary artery disease （CAD） in China.
Methods From December 2001 to April 2007, 8190 consecutive patients received the treatment with DES, 5412 patients completed one year follow-up： 2210 with sirolimus-eluting stent Cypher, 1238 with paclitaxel-eluting stent Taxus and 1964 with Chinese sirolimus-eluting stent Firebird, After two years of follow-up, there were 2176 patients （1245 Cypher, 558 Taxus and 373 Firebird）. All patients were treated with aspirin and clopidogrel over at least 9 months.
Results Among 8190 patients, 17 patients had acute stent thrombosis （0.24%）： 7 in the Cypher group, 4 Taxus and 6 Firebird; 23 patients had subacute stent thrombosis： 8 Cypher, 6 Taxus and 9 Firebird. The incidence of acute and subacute thrombosis was 0.49%： 0.50% Cypher, 0.63% Taxus and 0.41% Firebird. The incidence of late thrombosis at one year followup was 0.63%： 0.63% Cypher, 0.88% Taxus and 0.46% Firebird; at two year follow-up the incidence was 0.74%： 0.72% Cypher, 0.90% Taxus and 0.54% Firebird. There was no significant difference among three groups at 1 year and 2 years follow-up.
Conclusion The first generation DES in the treatment of complex lesions are safe and effective if patients are aggressively treated with dual antiplatelet agents.     

多个药物支架植入安全性和可行性的临床研究

目的 评估多药物支架植入术的近期疗效及安全性.方法 对我院从2004年6月到2005年12月共34例多个药物支架(≥3枚)植入术进行回顾性分析,对照组为单个支架植入组(n=64)和两支架植入组(n=53),随访术后6月冠状动脉内急性及亚急性血栓形成的发生率、再狭窄和心血管事件的发生率.结果 151例患者PCI治疗均成功.介入治疗1个月随访结果显示,多支架组、两支架组及单支架组均没有发生冠状动脉内血栓形成(P＞0.05),介入治疗6个月随访结果显示,再狭窄及心血管事件发生率均无统计学差异(P＞0.05).结论 多个药物支架植入治疗,并不增加近期血栓形成和心血管事件的发生率.     

Meta-analysis of stent thrombosis after drug-eluting stent implantation: 4-year follow-up

Background Drug-eluting stents （DES） are the most common device used in percutaneous treatment of coronary artery disease. Recently, there has been an increased concern regarding their safety profile, in particular the late and very late stent thrombosis rate compared to bare metal stents （BMS）. The aim of the study was to compare the reported incidence of late and very late stent thrombosis of DES and BMS in patients from published clinical studies with an extended follow-up period to four years.Methods A search strategy was developed to identify publications reporting on late or very late thrombosis of BMS and DES available through MEDLINE and Cochrane Library databases. Two independent reviewers appraised eligible studies and extracted data. Odds ratios （OR） were calculated for each outcome and presented with 95% confidence intervals （CI）.Results Fourteen randomized controlled trials, which were at least single blinded, were identified. There was no difference in the incidence of late and very late stent thrombosis in patients treated with DES compared with patients treated with BMS （late OR 0.55, 95%Cl 0.23-1.31 and late/very late OR=1.08, 95%CI 0.61-1.91）.Conclusions The safety profile of DES was similar to BMS in terms of stent thrombosis. We found no evidence of increased risk of late and very late thrombosis for DES.     

Late stent thrombosis: a not negligible issue after drug-eluting stent implantation

Drug-eluting stent （DES） has markedly reduced restenosis and the need for target lesion revascularization （TLR）. The safety profile of DES does not seem to differ from that of bare metal stent in the acute and subacute phases following coronary intervention. However, at World Congress of Cardiology 2006 a meta-analysis of randomized trials suggested that there was a small but significant increase in risk of death or Q-wave myocardial infarction throughout a period of 3 years after implantation of a Cypher stent possible due to late stent thrombosis） The study received wide attention and since then the long-term safety of DES has been questioned by the physicians, patients and societies.     

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.      

Morphologic characteristics of late stent malapposition after drug-eluting stents implantation by optical coherence tomography follow-up

Background Late stent malapposition was frequently observed after DES implantation, which has been associated with the occurrence of late stent thrombosis due to poor neointimal coverage. This study was designed to evaluate the frequency of late stent malapposition at least 1 year after different DESs implantation by optical coherence tomography （OCT）. Methods Angiographic and OCT examinations were given to 68 patients who had received total 126 various DESs implantation for at least 1 year to detect late stent malapposition. Malapposed strut distance （MSD）, malapposed strut area （MSA）, reference lumen area （RLA） and reference stent area （RSA） were checked with off-line OCT analysis. Results Totally 26 Cypher Select stents, 15 Taxus Liberte stents, 51 Partner stents and 34 Firebird I stents were examined. Among 68 patients who underwent DES implantation, 7 patients （10.3%） had late malapposition. Average RSA, MSA and MSD were （7.9=6？..8） mm2,（2.0＋1.6） mm2 and （590_＋_270） pm respectively. According to the MSA/RSA ratio 4 patients had slight malapposition, 2 patients had moderate malapposition and 1 patient had severe malapposition. Conclusions Late stent malapposition is detected frequently after implantation of DES, but if this predisposes to late stent thrombosis and requires any specific therapy needs to be further elucidated.     

药物洗脱支架与血管内放射治疗在支架内再狭窄中运用的Meta分析

目的 比较药物洗脱支架与血管内放射治疗在支架内再狭窄治疗中的疗效及安全性.方法 利用文献检索方法收集国内外治疗支架内再狭窄的对比研究,对符合入选条件的文献采用RevMan 5.1软件进行Meta分析.结果 入选13篇文献,共纳入病例2 312例,其中药物洗脱支架组1 259例,血管内放射治疗组1 053例.Meta分析显示:药物洗脱支架组再发支架内狭窄(P ＜0.000 01)、晚期管腔丢失(P ＜0.000 01)、靶血管血运重建(P=0.03)和主要不良心血管事件(P=0.004)均明显低于血管内放射治疗组.药物洗脱支架组晚期支架血栓发生率和死亡率与血管内放射治疗组相比差异均无统计学意义.结论 Meta分析显示,药物洗脱支架治疗支架内再狭窄在降低支架再次狭窄、减少晚期管腔丢失、靶血管血运重建方面明显优于血管内放射治疗,但不能减少晚期支架血栓形成及降低患者的死亡率.     

“真实世界”药物涂层支架（DES）植入后5年随访研究

目的研究第一代药物洗脱支架治疗冠心病远期（5年）临床疗效。明确晚期主要心血管事件的发生率。方法对2004年1月-12月就诊于我中心并成功植入DES的156例冠心病患者进行随访调查,为单中心非对照的登记研究,随访5年的主要心血管事件发生率。主要终点：观察主要不良心血管事件（Major Adverse Cardiac Events,MACE）发生情况;次要终点：心绞痛复发和非靶血管的血运重建。结果 156例冠心病DES植入者成功随访,随访时间（5.21±0.32）年。主要MACE发生32例（21%）,其中心原性死亡5例（3.2%,心原性猝死3例,心衰和急性心肌梗死各1例）,靶病变/靶血管的再次血运重建19例（12.2%）,再次非致命性心梗8例（5.1%）,心绞痛复发43例（27.6%）,其他血管血运重建及CABG治疗6例。脑出血、感染、肿瘤死亡各1例。Logistic回归分析显示氯吡格雷服用时间（P=0.016,OR=1.1,95%CI：1.018-1.188）和多支血管病变（P=0.039,OR=3.35,95%CI：1.06-10.55）是MACE发生的独立危险因素。结论多支血管病变者MACE发生率增加;服用氯吡格雷时间长者并未在MACE发生方面绝对获益。