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.     

药物洗脱冠状动脉支架术后血栓的防治

药物洗脱冠状动脉支架（DES）已成为冠心病介入治疗的里程碑。但是,尽管第一代DES比裸金属支架（BMS）明显降低了再狭窄率,美国心脏学会（ACC）2006年年会公布的巴塞尔支架效价比-晚期血栓事件试验（BASKET-LATE）研究结果显示,接受DES的患者术后6个月停用氯吡格雷后继续随访1年过程中发生死亡和心肌梗死的风险较BMS组高3倍,术后7～18个月晚期血栓事件发生率比BMS组增加1倍,提示停用氯吡格雷后DES治疗的患者迟发性（〉1年）血栓事件导致的不良事件风险增加。     

Incidence and predictors of definite stent thrombosis after coronary stent implantation

Background  Coronary stents are widely used in percutaneous coronary intervention (PCI) procedures. We aimed to explore the incidence, predictors and characteristics of stent thrombosis (ST) after coronary stent implantation in routine clinical practice.

Methods  From data of 18 063 consecutive patients who underwent successful stent implantation in Shenyang Northern Hospital from 2004 to 2010, we identified patients with definite ST (n=140) and control patients (n=280) matched on age, diagnosis, sex, current antiplatelet medication and stent type. The incidence, predictors and characteristics of ST after coronary stent implantation were investigated.

Results  The incidence of angiographically confirmed ST was 0.78% (140/18 063). The time distribution of ST was acute in 43 (30.7%), subacute in 50 (35.7%), and late in 47 (33.6%) patients. Binary Logistic regression analysis identified the angiotensin-converting enzyme inhibitor (ACEI) (odds ratio (OR)=0.472, 95% CI: 0.276–0.807, P=0.006) and heparin (OR=0.477, 95% CI: 0.278–0.819, P=0.007) were associated with an reduced risk of cumulative ST. Stent length (OR=1.042, 95% CI: 1.026–1.058, P <0.001), serum creatinine total (OR=1.020, 95% CI: 1.004–1.035, P=0.04), cholesterol (OR=1.267, 95% CI: 1.021–1.573, P=0.032), glucose (OR=1.086, 95% CI: 1.002–1.176, P=0.044), and platelet aggregation (OR=1.113, 95% CI: 1.075–1.154, P <0.001) were associated with an increased risk of cumulative ST.

Conclusion ST is associated with longer stent length and higher level of total cholesterol, glucose and platelet aggregation.

     

Two-year clinical outcome after successful implantation of drug-eluting and bare metal stents in diabetic patients: results from a real-world single center registry

Background Drug-eluting stents （DES） have revolutionized the field of interventional cardiology by dramatically improving clinical and angiographic outcomes. Patients with diabetes mellitus （DM） are associated with an increased risk of adverse clinical outcomes after a percutaneous coronary intervention （PCI）. Available information on the efficacy and safety of DES and bare metal stent （BMS） in diabetic patients remains scarce.
Methods From April 2004 to October 2006, 1565 patients with diabetes, who successfully underwent elective stenting at Fu Wai Hospital in Beijing, China, were enrolled in this study. All enrolled patients were assigned to a drug eluting stent group and a bare metal stent group. We obtained follow-up data： death, myocardial infarction （MI）, thrombus, target lesion revascularization （TLR）, and target vessel revascularization （TVR） at 30 days and 12 and 24 months, as defined by the Academic Research Consortium （ARC）. We calculated and compared all the unadjusted cumulative frequencies of the various adverse events in the two groups. Cox＇s proportional-hazards models adjusted with the propensity score were used to assess the relative risks of all the outcome measures at 24 months.
Results At 24 months, all ARC defined stent thrombosis in the two groups were similar; at 30 days, a more definite thrombosis was found in the BES group （0.08% vs 0.81%, P=0.016）. Patients treated with DES showed a significant lower risk of TLR （3.88% vs 10.89%; hazard ratio （HR） 0.159 （95% CI： 0.151-0.444）, P 〈0.001）, TVR （5.48%vs 11.69%; HR 0.383 （95% CI： 0.232-0.633）, P 〈0.001）, and any revascularization （12.47% vs 18.55%; HR 0.555 （95% CI： 0.370-0.831）, P=0.0004） at 24 months. No significant difference was apparent in terms of all-cause mortality, MI, and all-cause mortality/MI.
Conclusions In contemporary society＇s large, diabetic population, the use of DES is associated with long-term significant reductions in the risks of TLR, TVR, and any revascularization. There is no significant difference in all-cause mortality, MI, and thrombosis between DES and BMS in the patients with diabetes at 24-month follow-up.     

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.      

Clinical outcome after management of unprotected left main in-stent restenosis after bare metal or drug-eluting stents

Background Implantation of either bare metal stent （BMS） or drug-eluting stent （DES） has been used in every day practice for patients with unprotected left main stenosis （UPLMS）. There are still a lack of data regading the subsequent results of UPLMS in-stent restenosis （ISR）. The present study aimed at determing the clinical outcome of UPLMS ISR patients after implantation of either BMS or DES.Methods Patients with UPLMS ISR after stenting were included. The primary endpoint was the cumulative major adverse cardiac events （MACE）, including cardiac death, myocardial infarction （Ml）, and target vessel revascularization （TVR）.Results UPLMS ISR rate was 14.8% （n=73, 15.7% after BMS, 14.5% for DES） after average of （3.89±2.01） years （range from 1 to 10.5 years） follow-up. Angiographic follow-up between 6-8 months was available in 85.3%. Of these,repeat percutaneous coronary intervention （PCI） was used in 62 （84.9%） patients, with medicine only in 9 （12.4%） and coronary artery bypass graft （CABG） in 2 （2.7%）. Most repeat PCI patients were with unstable angina （87.0%）, and had decreased left ventricular ejection fraction （（42.58±5.12）%）, fewer focal/ostial left circumflex branch （LCX） lesions, in relative to medicine only group. After （31.9±23.3） months, the MACE, Ml, TVR and cardiac death were 31.5%, 1.4%, 24.1% and 8.2%, respectively. Definite and possible stent thrombosis occurred in 1 （1.4%） patient.Conclusions Medical therapy for asymptomatic isolated ostial LCX was safe. Repeat PCI for UPLMS ISR was associated with acceptable early and short-term clinical outcome. Further study was needed to elucidate the role of CABG in treating UPLMS ISR.     

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.     

Impact of weight gain following smoking cessation on one-year outcome after drug-eluting stent implantation

Background  Weight gain following smoking cessation increases cardiovascular risk, but its effects on prognosis after percutaneous coronary intervention (PCI) remain unclear. This study aimed to investigate the relationship between weight gain post smoking cessation and one-year clinical outcome in patients who underwent PCI with drug-eluting stent (DES).

Methods  A total of 895 consecutive male smoking patients were divided into quitters (n=437) and continuers (n=458) according to their smoking status after PCI. Weight gain, major adverse cardiac events (MACE, including cardiac deaths, myocardial infarction and revascularization), and recurrent angina were recorded during follow-up for one year.

Results  Average weight gain in quitters was more than that in continuers (1.5 kg vs. –0.03 kg, P <0.001). Weight was unchanged or increased by more than 1.5 kg in 78.17% of continuers, while 50.57% of quitters had a weight gain of less than 1.5 kg. Compared with continuers, MACE in quitters was significantly reduced after PCI (6.12% vs. 4.81%, P=0.049), especially recurrent angina (13.97% in continuers vs. 9.84% in quitters, P=0.027). After adjusting for weight gain and other factors, smoking cessation was independently associated with a lower risk of MACE and recurrent angina (OR=0.73, P=0.035). However, weight gain >1.5 kg (OR=1.55, P=0.026) could curtail the benefits from smoking cessation.

Conclusions  Weight gain may reduce the benefits of smoking cessation after PCI with DES implantation. Thus, although smoking cessation is recommended after PCI, weight control should also be highly encouraged for these patients.     

“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。     

非顺应球囊后扩张对置入药物洗脱支架预后的影响

目的评估使用非顺应性球囊后扩张对经置入药物洗脱支架冠状动脉粥样硬化性心脏病(以下简称冠心病)患者的疗效。方法回顾性分析2011年1月至2011年5月共356例行药物洗脱支架植入且使用非顺应性球囊后扩张的患者,采用倾向性评分抽取同期356例行药物洗脱支架植入术而未后扩张的患者与之1∶1匹配。结果 2组在年龄、性别、临床表现、主要危险因素及冠状动脉病变特征方面比较,差异无统计学意义(P>0.05),具有可比性。平均随访时间18个月,后扩张组主要不良心血管事件(major adverse cardiac events,MACE)明显低于未后扩张组(10.1%vs 15.7%,P=0.020),主要是靶血管重建(6.2%vs10.7%,P=0.010)、支架内血栓(1.1%vs 3.7%,P=0.030)发生率比较,差异有统计学意义(P<0.05),而心肌梗死(3.9%vs4.6%,P=0.700)、死亡(1.1%vs 1.7%,P=0.760)比较,差异没有统计学意义。结论冠心病患者置入药物洗脱支架后使用非顺应性球囊后扩张安全,可改善患者的临床预后。     

Comparison of the incidence of late stent thrombosis after implantation of different drug-eluting stents in the real world coronary heart disease patients: three-year follow-up results

Background Late stent thrombosis （LST） is still concerned by interventions cardiologists in daily clinical practice. This study aimed to compare the incidence of LST after implantation of different drug-eluting stents （DES） in coronary heart disease （CHD） patients in the real world.Methods From December 2001 to February 2009, a total of 11 875 consecutive CHD patients undergone DES implantation were enrolled in this single-center registery study. Patients with acute ST-segment elevation myocardial infarction, mixed DES implantation, restenosis lesions, and patients who could not take dual antiplatlet medication and those who were contraindicated for coronary interventional treatment were excluded. All patients were treated with completed dual antiplatelet medications for at least 9 months after DES deployment. The follow-up was completed by outpatient visits, letter correspondence, phone calls and coronary angiography. Definite LST was diagnosed auording to the Academic Research Consortium （ARC） definition.Results Cypher or Cypher Select stents were implanted in 4104 cases, Taxus or Taxus Liberty stents in 2271 cases and Firebird stents （Chinese rapamycin-eluting stents） in 5500 cases. One-year follow-up was completed in 9693 patients, including 3346 cases with Cypher or Cypher Select stents, 1529 cases with Taxus or Taxus Liberty stents and 4818 cases with Firebird stents. Two- and three-year follow-up results were obtained in 7133 and 4353 patients, respectively, including 2410 and 1760 cases with Cypher or Cypher Select stents, 1285 and 900 cases with Taxus or Taxus Liberty stents as well as 3438 and 1693 cases with Firebird stents. One-year follow-up results showed that the incidence of LST was 1.08% in patients with Cypher or Cypher Select stents, 1.24% in those with Taxus or Taxus Liberty stents and 0.71% in those with Firebird stents; there was no significant difference between those with Cypher or Cypher Select and Firebird stents, but there was significant difference between those with Taxus or Taxus Liberty and Firebird stents （P=0.044）. The incidence of LST at the 2- and 3-year follow-up was 1.33% and 1.70% in those with Cypher or Cypher Select stents, 1.40% and 1.70% in those with Taxus or Taxus Liberty stents, and 0.83% and 0.95% in those with Firebird stents, respectively. There were no significant differences among the three groups.Conclusions This study indicates that first-generation DES are acceptable to treat complex coronary lesions, and there is no significant difference of LST for three different DES.     

Intravascular ultrasound assessment of the incidence and predictors of edge dissections and intramural hematomas after drug-eluting stent implantation

Objective We used intravascular ultrasound (IVUS) to assess incidence, predictors, morphology, and angiographic findings of edge dissections and intramural hematomas after drug-eluting stent (DES) implantation. Methods We studied 887 patients with 1 045 non-in-stent restenosis lesions in 977 native arteries undergoing DES implantation with IVUS imaging, and compared the dissected stent end to the non-dissected stent end. Results Eighty-two dissections were detected; 51.2% (42/82) involved the proximal and 48.8% (40/82) the distal stent edge. When compared to the non-dissected stent end, residual plaque area [(8.0±4.3) mm2 vs (5.2±3.0) mm2, P<0.01], plaque burden [(52±12)% vs (36±15)%, P<0.01], plaque eccentricity (8.4±5.5 vs 4.0±3.4, P<0.01), and stent edge symmetry (1.17±0.11 vs 1.14±0.08, P=0.02) were larger; plaque burden≥50% was more frequent (62% vs 17%, P<0.01) and calcium deposits (52.5% vs 35.6%, P=0.03) more common; and the lumen/stent area (0.86±0.16 vs 1.02±0.18, P<0.01) was smaller in the stent dissected end. Independent predictors of stent edge dissection were residual plaque eccentricity (OR=1.3, P<0.01) and residual plaque burden≥50% (OR=7.3, P<0.01). Intramural hematomas occurred in 34.1% (28/82) of dissections.Independent predictors of intramural hematomas were plaque eccentricity (OR=1.4, P=0.005), plaque burden≥50% (OR=7.1, P=0.02), and mean lumen diameter to stent diameter ratio (OR=0.37, P=0.04).Concluslon IVUS identified edge dissections after 9.4% of DES implantations. Residual plaque eccentricity and significant plaque burden predicted coronary stent edge dissections. Dissections in less diseased reference segments with an arc of normal vessel wall (greater plaque eccentricity) more often evolved into an intramural hematoma.     

冠脉药物涂层支架的发展

经皮经腔冠脉介入术(percutaneous transluminal coronary intervention，PCI)已经超过冠脉旁路移植手术(coronary artery bypass grafting，CABG)，并成为治疗冠脉疾病最常用的治疗方法。但是，球囊扩张术及传统支架植入术后短、中期再狭窄的发生率达5％～60％，严重限制了PCI的发展。PCI术后再狭窄发生的主要原因是血管壁弹性回缩和血管     

Subacute thrombosis after stents implantation in a patient with two adjacent coronary artery aneurysms

Coronary artery aneurysm is an uncommon disease. When it is associated with significantly obstructive coronary artery disease, percutaneous transluminal coronary angioplasty with graft-coated stent implantation usually provides favorable results. Non-coated stents may have the potential risk of thromboembolism. We present a patient with unstable angina who received elective balloon angioplasty and non-coated stent implantations in two adjacent aneurysms. Two episodes of subacute stent thrombosis occurred subsequently at the two different aneurysmal lesions respectively, which were resolved by repeat balloon angioplasty. Post-procedural intravenous heparin infusion is strongly suggested to prevent the development of stent thrombosis. Long-term oral warfarin is also suggested for prophylaxis of recurrent thromboembolic events.