Late thrombosis following treatment of in-stent restenosis with drug-eluting stents after discontinuation of antiplatelet therapy.

Drug-eluting stent usage has become commonplace for the percutaneous treatment of de novo coronary lesions, but the safety and efficacy profile for their evolving usage in restenotic lesions is largely unknown. We report three cases of angiographically confirmed drug-eluting stent thrombosis following treatment of restenotic lesions that occurred late (193, 237, and 535 days) and shortly after interruption of antiplatelet therapy. All three patients suffered ST elevation myocardial infarction, and there was one death. Further studies are necessary to better define the associated risk and ideal duration of antiplatelet therapy necessary in this cohort of patients with restenotic lesions.     

Recurrent late drug-eluting stent thrombosis upon discontinuation of antiplatelet therapy

Stent thrombosis is a rare but serious complication of percutaneous coronary intervention. Stent thrombosis usually occurs early after stent implantation but can occasionally occur late, especially when drug-eluting stents are used. We report a case of recurrent late paclitaxel-eluting stent thrombosis (8 and 21 months after initial stent implantation) upon discontinuation of dual antiplatelet therapy.     

冠心病介入术后双联抗血小板治疗持续时间的研究

目的:对置入佐他莫司洗脱支架的冠心病患者双联抗血小板治疗(DAPT)12个月后,继续延长治疗时间能否获益进行分析。方法:回顾性分析2006年9月至2009年6月于北京安贞医院心内科置入佐他莫司洗脱支架的患者,按照DAPT的时间分为:DAPT12个月组和DAPT>12个月组,通过门诊或电话随访,评价术后患者主要不良心脑血管病事件(死亡、心肌梗死、卒中和靶血管再次血运重建发生率),观察两组患者以上各终点差异是否有统计学意义。结果:随访平均(28.4±7.4)个月,共915例患者纳入分析,DAPT 12个月组362例,DAPT>12个月组553例。两组主要心血管事件(MACCE)发生率分别为3.6%和4.3%,Log rank P=0.87血运重建(TVR)分别为2.2%和2.5%,Log rank P=0.97,死亡、心肌梗死、卒中各终点两组间差异均无统计学意义。结论:对于置入佐他莫司洗脱支架的患者,与12个月时停用DAPT仅使用阿司匹林比较,12个月后继续使用DAPT未能显示出优势,两者无明显差异,12个月时停用氯吡格雷安全有效。     

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents

Background Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Methods Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug(clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events(a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.Results A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo.Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis(0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P 0.001) and major adverse cardiovascular and cerebrovascular events(4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85];P 0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo(2.1% vs. 4.1%; hazard ratio, 0.47; P 0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group(hazard ratio, 1.36 [95% CI, 1.00 to 1.85];P = 0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment(2.5% vs. 1.6%, P = 0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Conclusions Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding.(Funded by a consortium of eight device and drug manufacturers and others; DAPT Clinical Trials.gov number, NCT00977938.)(From: N Engl J Med 2014; 371:2155-2166 December 4, 2014DOI: 10.1056 / NEJMoa1409312)     

Impact of prolonged dual antiplatelet therapy on patients after drug-eluting stents implantation

Background Impact of dual antiplatelet therapy beyond 12 months on patients implanted with DES remains unsolved.Methods From January 2010 to June 2011,1873 patients who have been taking DAPT and free from death,myocardial infarction,stroke,repeat coronary revascularization,stent thrombosis,and major or minor bleeding according to TIMI criteria for 12 months after implantation of DES were randomly assigned to continuous (prolonged DAPT group) or discontinuous (standard DAPT group) clopidogrel (75 mg/day).The primary outcome was major adverse cardiovascular events (MACEs) which compose of death,nonfatal myocardial infarction (MI),nonfatal stroke,target vessel revascularization (TVR) or stent thrombosis (ST) at 180 days.Results There was no significant difference in the incidence of 180-day MACEs between prolonged DAPT group and standard DAPT group (8.98 % versus 10.13 %,respectively,P=0.400).The frequency of major bleeding was 0.64 % in prolonged DAPT arm and 0.43% in standard DAPT arm (P=0.523),that of minor bleeding was 3.32 % versus 2.87 % (P=0.585),respectively.Conclusions Prolonged DAPT beyond 12 months neither improve prognosis nor increase risk of bleeding in patients implanted with DES.     

Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents.

OBJECTIVES: We sought to define the incidence of late clinical events and late stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal stents (BMS) after the discontinuation of clopidogrel as well as their timing and outcome. BACKGROUND: There is growing concern that delayed endothelialization after DES implantation may lead to late stent thrombosis and related myocardial infarction (MI) or death. However, event rates and outcomes after clopidogrel discontinuation versus BMS are unknown. METHODS: A consecutive series of 746 nonselected patients with 1,133 stented lesions surviving 6 months without major events were followed for 1 year after the discontinuation of clopidogrel. Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent Kosten Effektivit?ts Trial). The primary focus of this observation was cardiac death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between DES and BMS patients. However, after the discontinuation of clopidogrel (between months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS implantation. Target vessel revascularization remained lower after DES, resulting in similar rates of all clinical events for this time period (DES 9.3%, BMS 7.9%). Documented late stent thrombosis and related death/target vessel MI were twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events occurred between 15 and 362 days after the discontinuation of clopidogrel, presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of clopidogrel, the benefit of DES in reducing target vessel revascularization is maintained but has to be balanced against an increase in late cardiac death or nonfatal MI, possibly related to late stent thrombosis.     

Very late thrombosis after drug-eluting stents.

Stent thrombosis is a rare but potentially fatal complication of percutaneous treatment of coronary disease. Its occurrence after drug eluting stent (DES) placement has raised concerns, especially when it occurs late after the stent implantation. The mechanisms of late thrombosis after DES have yet to be completely understood. By means of serial angiography and intravascular (IVUS) images we described a relatively new and unusual vessel response to drug-eluting stents (e.g. huge positive remodeling in all vessel extension), leading to impressive late-acquired incomplete stent apposition and finally causing stent thrombosis and acute myocardial infarction. After describing the two cases, one after Cypher stent implantation and one after Taxus stent implantation, we briefly reviewed the literature available on stent thrombosis with special emphasis on its late occurrence.     

替罗非班对复杂冠脉病变植入药物洗脱支架后亚急性血栓的影响

目的评价替罗非班对冠脉复杂病变介入治疗的安全性及对药物洗脱支架内亚急性血栓的影响。方法回顾性分析自2005年1月至2008年12月连续在解放军总医院老年心血管病研究所住院并行冠脉介入治疗的复杂冠脉病变患者289例,根据围手术期替罗非班使用率的多少分为第一阶段（即使用率较少组）171例和第二阶段（即使用率较多组）118例,分别记录两个不同阶段患者的临床特征、冠脉病变情况、支架植入情况、替罗非班使用率、出血并发症及亚急性血栓发生情况,观察并分析替罗非班对复杂冠脉病变行介入治疗的安全性及对支架内亚急性血栓形成的影响情况。结果两个阶段的冠心病患者的临床资料无统计学差异,两个阶段冠脉病变为B2和C型病变的患者分别为108、63例比78、40例,无统计学差异,两个阶段平均植入支架的数量分别为（3.1±1.3）枚和（2.9±1.2）枚,平均植入支架的总长度分别为（34.4±14.3）mm和（36.5±16.3）mm,均无统计学差异。两个阶段替罗非班使用率分别为15.2%比62.7%,有显著性差异。两个阶段出血并发症的发生率分别为4.67%和4.23%,无统计学差异。两个阶段支架内亚急性血栓的发生率分别为1.75%和0%,无统计学差异,但有减少的趋势。结论复杂冠脉病变植入药物洗脱支架的围手术期使用替罗非班是安全的,且降低了支架内亚急性血栓发生的趋势。     

三联抗血小板在老年复杂冠状动脉介入患者术后有效性和安全性对照研究

目的评价西洛他唑、氯吡格雷和阿司匹林三联抗血小板药物在老年复杂冠状动脉介入患者植入多枚药物洗脱支架（DES）术后的疗效和安全性。方法2006年3月至2009年9月人选128例冠状动脉B2／C型病变、采用多DES植入的老年（65-75岁）患者。所有入选患者术后随机分为两组：标准化治疗组（对照组,n=67）和三联抗血小板治疗组（试验组,n=61）。3个月后所有患者接受标准化治疗直至术后12个月。观察两组患者临床特征、冠状动脉病变特点以及支架植入特征,平均随访（20．4±5．1）个月主要心血管事件、支架内血栓和出血事件。结果试验组心肌梗死及再次血运重建发生率均显著低于对照组（6．56％vs11．94％,P=0．043;6．56％vs13．43％,P=0．042）。两组全因病死率差异无统计学意义（1．64％vs2．99％,P=0．615）。试验组主要终点事件绝对风险较对照组降低8．07％（P=0．043）。试验组近期、远期支架内血栓事件发生率显著低于对照组（0．00％vs2．99％,P=0．050;1．64％vs4．48％,P=0．048）：两组间出血发生率差异无统计学意义（P〉0．05）。结论三联抗血小板药物可降低复杂冠状动脉介入老年患者术后发生主要不良心血管事件、支架内血栓形成的风险,并且不增加出血事件的发生风险。     

Stent thrombosis and drug-eluting stents

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis.Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES.     

药物洗脱支架与迟发支架血栓——证据、程度与共识

继单纯球囊扩张术、支架置入术之后,药物洗脱支架(DES)已成为冠心病介入治疗发展史的新里程碑,根除再狭窄这个普通支架的“致命软肋(achilles'heel)”终于崭露曙光。历经几年的“欣喜”与“狂热”,     

Late angiographic stent thrombosis (LAST) events with drug-eluting stents

OBJECTIVES: We sought to describe the incidence of late angiographic stent thrombosis (LAST) events in an unselected drug-eluting stent (DES) population. BACKGROUND: Concerns have been raised that LAST may be a potential limitation of DES. METHODS: We have previously reported the angiographic incidence of early stent thrombosis (1.0%) in this prospective cohort of 2,006 patients treated with either sirolimus-eluting stents (SES) (n = 1,017) or paclitaxel-eluting stents (PES) (n = 989). We continued long-term follow-up to determine the incidence of LAST events, defined as angiographically proven stent thrombosis associated with acute symptoms more than 30 days after DES implantation. All patients had at least 1 year of follow-up, mean duration 1.5 years. RESULTS: There were eight angiographically confirmed LAST events in seven patients: three with SES (at 2, 25, and 26 months) and five with PES (at 6, 7, 8, 11, and 14.5 months). Three cases were related to complete cessation of antiplatelet therapy, two cases occurred while patients were on aspirin therapy within one month of cessation of clopidogrel, and three cases occurred at a time when patients were apparently clinically stable on aspirin monotherapy. We observed no cases of LAST in patients who were on dual antiplatelet therapy. Two deaths occurred directly as a result of LAST. CONCLUSIONS: Angiographically proven late stent thrombosis occurs with an incidence of at least 0.35% (95% confidence limits 0.17% to 0.72%) in patients treated with DES. Importantly, it may also occur when patients are stable on antiplatelet monotherapy.     

Very late drug-eluting stent thrombosis after nonsteroidal anti-inflammatory drug treatment despite dual antiplatelet therapy

BACKGROUND:

Drug-eluting coronary stent implantation emerged as a safe and effective therapeutic approach by preventing coronary restenosis and reducing the need for further revascularization. However, in contrast to bare metal stents, recent data suggest a unique underlying pathology, namely late coronary stent thrombosis and delayed endothelial healing.

OBJECTIVE:

To report a case of very late coronary stent thrombosis (834 days after implantation) requiring repeat urgent target-vessel revascularization. Importantly, six days before the acute coronary event, combined nonsteroidal anti-inflammatory drug therapy was initiated.

RESULTS:

Although a dual antiplatelet regimen was continuously maintained, aggregation measurements indicated only partial antiplatelet effect, which returned to the expected range when nonsteroidal anti-inflammatory drugs were omitted.

CONCLUSIONS:

The observation indicates that, even 834 days after drug-eluting stent implantation, effective combined antiplatelet therapy might be crucial in certain individuals and the possible impact of drug interactions should not be underestimated. Further efforts should focus on the challenging task of identifying patients or medical situations with prolonged, increased risk of stent thrombosis.