The role of drug-eluting stents for the treatment of coronary chronic total occlusions

First generation drug-eluting stents (DES) had a major impact on our capacity to percutaneously treat coronary chronic total occlusions by significantly reducing the risk for in-stent restenosis compared to bare metal stents. Second generation drug-eluting stents further improved our capacity to treat these complex lesions by providing improved deliverability and enhanced efficacy and safety. The ongoing development of bioabsorbable stents will likely be the next major advancement to improve the durability of chronic total occlusion interventions.     

佐他莫司药物洗脱支架与雷帕霉素药物洗脱支架治疗冠心病临床疗效与安全性的Meta分析

目的比较佐他莫司药物洗脱支架（ZES）与雷帕霉素药物洗脱支架(SES)在经皮冠状动脉介入治疗术(PCI)中的临床疗效与安全性差异。方法检索Pubmed、Embase、Chocorane library、Science Direct、CNKI数据库、中国生物医学文献数据库以及相关网站(http://scholar.google.com/),收集建库至2016年1月31日公开发表的有关ZES与SES疗效和安全性比较的随机对照实验（RCTs）,按Chochrane系统评价手册对文献质量进行严格评价,对纳入的RCTs进行资料提取,采用RevMen 5.3软件进行Meta分析。结果共纳入9项RCTs,共6 672例患者,其中ZES组3 434例,SES组3 238例。结果显示：ZES组与SES组总病死发生率（RR=0.99,95%CI=0.83～1.19,P=0.93）、心源性猝死率（RR=0.86,95%CI=0.63～1.19,P=0.37）、主要不良心脏事件发生率（RR=1.05,95%CI=0.93～1.20,P=0.43）、心肌梗死发生率（RR=0.84,95%CI=0.68～1.02,P=0.08）、靶血管血运重建率（RR=1.19,95%CI=0.99～1.42,P=0.06）、支架内血栓发生率（RR=0.82,95%CI=0.46～1.46,P=0.50）差异无统计学意义,靶病变血运重建率（RR=1.49,95%CI=1.18～1.89,P=0.0008）差异有统计学意义。结论现有证据表明,两种药物洗脱支架治疗冠状动脉粥样硬化性心脏病（冠心病）的总死亡发生率、心源性猝死发生率、主要不良心脏事件发生率、心肌梗死发生率、靶血管血运重建率、支架内血栓发生率相似;与ZES相比,SES能明显降低支架术后靶病变血运重建的发生率,但敏感性分析显示该结果不稳定。     

Everolimus-eluting stents for treatment of chronic total coronary occlusions

Background  

After successful recanalization of a coronary chronic total occlusion (CTO) the risk for restenosis and subsequent need for repeat intervention is high. Everolimus-eluting stents (EESs) were associated with low rates of restenosis, reintervention and stent thrombosis in non-occluded lesions. We sought to determine the antiproliferative impact of the everolimus-eluting Xience V stent in CTOs.     

曲美他嗪对冠状动脉慢性完全闭塞病变经皮冠状动脉介入治疗术后心功能的影响

目的探讨曲美他嗪对冠状动脉慢性完全闭塞病变患者经皮冠状动脉介入治疗(PCI)术后心功能的影响。方法经冠状动脉造影确诊冠状动脉慢性完全闭塞病变患者90例,其中43例行PCI术,术后分为两组:A组23例,B组20例;未行PCI术47例,分为两组:C组25例,D组22例。A组、C组曲美他嗪口服,20mg,3次/d;B组、D组不服用曲美他嗪。4组均给予冠心病常规治疗。治疗跟踪观察12个月,其中A、B、C组各有1例、D组有2例死亡,剔除。比较4组治疗12个月前后超声心动图变化。结果A、B和C组治疗前后心功能均有明显改善,各组心功能超声学参数治疗后与治疗前比较差异有统计学意义(P0.05);A组治疗后的心功能较B组治疗后的心功能改善更明显,A组治疗后心功能超声学参数与B组治疗后比较差异有统计学意义(P0.05)。结论曲美他嗪能进一步改善冠状动脉慢性完全闭塞病变患者PCI术后的心功能。     

Zotarolimus-eluting vs. sirolimus-eluting coronary stents in patients with and without acute coronary syndromes: a SORT OUT III substudy

Eur J Clin Invest 2012; 42 (10): 1047-1054 ABSTRACT: Objectives: To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial. Background: Currently, only limited data allow direct comparison of clinical outcomes among patients with acute coronary syndrome treated with a second-generation drug-eluting stent (DES) eluting zotarolimus vs. a first-generation DES eluting sirolimus. Methods: Patients with acute coronary syndrome (n?=?1052) were randomized to treatment with zotarolimus-eluting (n?=?506) or sirolimus-eluting (n?=?546) stents and followed for 18?months. The primary composite endpoint, major adverse cardiac events (MACE), was defined as a composite of cardiac death, myocardial infarction or target vessel revascularization. Results: Zotarolimus-eluting stent treatment compared to sirolimus-eluting stent treatment was associated with increased rates of MACE (8·7% vs. 5·0%; hazard ratio (HR), 1·78; 95% confidence interval (CI), 1·10-2·88; P?=?0·02) and TVR (6·8% vs. 3·9%; HR, 1·77; 95% CI, 1·03-3·04; P?=?0·04), while all-cause death, cardiac death, myocardial infarction and definite stent thrombosis did not differ significantly. In the same trial, stable angina pectoris patients (n?=?1206) were randomized to zotarolimus-eluting (n?=?614) and sirolimus-eluting (n?=?592) stents with similar results. Conclusions: With and without acute coronary syndromes, patients treated with the sirolimus-eluting stent had better clinical outcomes than those treated with the zotarolimus-eluting stent.     

杂交策略治疗冠状动脉慢性完全闭塞病变的有效性和安全性

目的 探讨药物洗脱支架（drug-eluting stent, DES）联用药物涂层球囊（drug-coated balloon, DCB）的杂交策略治疗冠状动脉慢性完全闭塞（chronic total occlusion, CTO）病变的有效性和安全性。方法 连续纳入2021年9月至2022年9月在复旦大学附属中山医院确诊为CTO并采用单纯DES植入或杂交策略治疗的369例患者，分为DES组（n=220）和杂交策略组（n=149）。比较两组患者的临床基线信息、介入手术特征、术后定量冠状动脉造影（quantitative coronary angiography, QCA）参数和定量血流分数（quantitative flow ratio, QFR）。随访术后1个月内主要不良心血管事件（major adverse cardiovascular events, MACE）发生率。结果 369例患者的369个病变以前降支病变（44.7%）和右冠状动脉病变（43.1%）为主。与DES组相比，杂交策略组植入支架数[1.67±0.66 vs 2.00±0.81, P<0.001]和植入支架...     

Reduced sirolimus systemic exposure and improved bioresorbable polymer properties: new allies for the treatment of patients with coronary artery disease

This prospective, first‐in‐man, open‐label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug‐eluting stent implantation (coated with sirolimus and bioabsorbable co‐polymer) in patients with de novo coronary artery disease (the TCD‐10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6‐month angiographic and up to 12 months clinical follow‐up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9–41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0–105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time–concentration curve, was 8.3 ng h/mL (range 6.47–28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity.     

The evolution of coronary stents

Introduction: Percutaneous coronary intervention (PCI) is 40 years old this year. From its humble beginnings of experimental work, PCI has transitioned over years with coronary artery stenting now a standard medical procedure performed throughout the world.

Areas covered: The conversion from plain old balloon angioplasty (POBA) to the present era of drug eluting stents (DES) has been driven by many technological advances and large bodies of clinical trial evidence. The journey to present day practice has seen many setbacks, such as acute vessel closure with POBA; rates of instant restenosis with bare metal stents (BMS) and more recently, high rates of stent thrombosis with bioabsorbable platforms. This work discusses POBA, why there was a need for BMS, the use of inhibiting drugs to create 1^st generation DES, the change of components to 2^nd generation DES, the use of absorbable drug reservoirs and platforms, and possible future directions with Prohealing Endothelial Progenitor Cell Capture Stents.

Expert commentary: This paper reviews the evolution from the original pioneering work to modern day practice, highlighting landmark trials that changed practice. Modern day contemporary practice is now very safe based on the latest drug eluting stents and supported by large datasets.     

急性ST段抬高心肌梗死患者应用进口及国产雷帕霉素洗脱支架疗效分析

目的 观察进口及国产雷帕霉素洗脱支架(Cypher与Firebird)在急性ST段抬高心肌梗死(ST-segmentelevation myocardial infarcation,STEMI)急诊经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)中的疗效及安全性.方法 选择有ST段抬高或新出现左束支传导阻滞(LBBB)急性心肌梗死、发病在12小时内或虽时间大于12小时但症状持续存在者302例;随机分为3组,即裸支架(bare metal stent,BMS)组98例、Cypher支架组103例和Firebird支架组101例;随访6～9个月,比较3组支架术后近期及远期疗效.结果 支架植入术前3组患者临床指标及冠状动脉病变情况比较差异均无统计学意义,术后住院及随访过程中主要不良心脏事件(major adverse cardiac events,MACE)发生率比较差异无统计学意义,复查冠状动脉造影,3组靶血管再狭窄率、血运重建率比较差异无统计学意义;3组支架内最小管腔内径(2.73±0.36)mm vs(2.95±0.19)mm、(2.94±0.20)mm,节段内最小管腔内径(2.61±0.29)mm vs(2.88±0.23)mm、(2.89±0.19)mm,支架内晚期管腔丢失(0.28±0.11)mm vs(0.03±0.09)mm、(0.04±0.10)mm,节段内晚期管腔丢失(0.25±0.17)mm vs(0.08±0.12)mm、(0.10±0.15)mm,裸支架组与Cypher支架组及Firebird支架组比较差异均有统计学意义(P＜0.05或P＜0.01),而Cypher支架组及Firebird 支架组比较差异均无统计学意义(P＞0.05).结论 雷帕霉素药物涂层支架(Cypher与Firebird)在急性ST段抬高心肌梗死(STEMI)患者急诊PCI中应用是安全有效的,较裸支架可明显减少管腔狭窄,降低支架内及节段内晚期管腔丢失;进口及国产雷帕霉素药物涂层支架(Cypher与Firebird)具有相同的临床疗效.     

介入治疗对冠状动脉慢性闭塞病变患者的远期效果

目的 探讨冠状动脉（冠脉）慢性闭塞病变（CTO）介入治疗成功对患者生活质量及预后的影响.方法 经皮冠脉介入治疗CTO 87例,57例成功开通闭塞冠脉并置入支架（开通组）,30例闭塞冠脉未开通（未开通组）.观察两组患者生活自理能力、生活质量及预后.结果 两组临床随访6～60个月,开通组的生活质量明显优于未开通组,死亡率无显著性差异.结论 介入治疗可改善冠脉CTO患者的临床症状及生活质量.     

国产西莫罗司洗脱支架和新型紫杉醇洗脱支架在冠状动脉病变治疗中的对比研究和1年随访

目的比较国产西莫罗司洗脱支架(EXCEL)和新型紫杉醇洗脱支架(TAXUS Liberte)在临床使用的有效性和安全性。方法符合行冠状动脉疾病介入治疗的患者,随机选择EXCEL和TAXUS Liberte支架治疗,其中EXCEL组55例,TAXUS组51例。比较两组的基础临床资料、冠状动脉造影参数,术后1年内随访死亡、心肌梗死、支架内血栓和靶血管血运重建等不良事件,部分患者6~12月内冠状动脉造影随访,比较再狭窄率、晚期管腔丢失。结果两组基本临床参数,支架植入前冠状动脉造影参数差异无统计学意义(P>0.05)。两组死亡、心肌梗死、支架内血栓和靶血管血运重建等单个不良事件差异亦无统计学意义(P>0.05)。总不良事件EXCEL组1.8%,TAXUS组11.8%,两者比较差异有统计学意义(P<0.05)。造影随访,EXCEL组晚期管腔丢失(0.15±0.10)mm,TAXUS组是(0.26±0.08)mm,差异有统计学意义(P<0.01)。结论两种支架在临床均显示了较高的安全性和较好的有效性,可以作为介入治疗的一线选择,国产EXCEL支架在某些方面更有优势,值得推广。     

国产Firebird支架与Cypher支架在急性心肌梗死患者中的临床对比研究

目的 通过对比研究的方法评价国产Firebird雷帕霉素涂层支架与进口Cypher雷帕霉素涂层支架在急性心肌梗死患者中应用的安全性和有效性.方法 选择我院2004年12月至2006年2月诊断为急性ST段抬高型心肌梗死且发病12小时以内患者中接受Firebird支架的患者38例(Firebird组),接受Cypher支架治疗的患者43例(Cypher组).观察两组住院期间和6个月随访期间的心血管事件及支架内再狭窄的发生情况.结果 住院期间Firebird组无急性、亚急性血栓形成及心绞痛事件发生,9例术后6个月复查冠状动脉造影(3例有心绞痛事件)均未见支架内再狭窄;Cypher组2例于术后复发胸痛,原ST段抬高导联再次抬高,急诊冠状动脉造影示亚急性血栓形成,再次开通.8例术后6个月复查冠状动脉造影(4例有心绞痛事件)1例显示支架内再狭窄,再次植入药物支架.两组各有3例患者心绞痛事件与非支架血管有关.结论 国产Firebird支架在急性心肌梗死患者中应用具有同Cypher支架一致的安全性和有效性.     

Assessment of the presence and extent of coronary collateralization by coronary computed tomographic angiography in patients with total occlusions

Coronary computed tomography angiography (CTA) may be helpful to manage patients with chronic coronary occlusions. The aim of this study was to determine the sensitivity and specificity of CTA to detect the presence and extent of coronary collaterals as compared to invasive coronary angiography (ICA). We retrospectively evaluated 26 patients who underwent both coronary CTA and ICA within 3 weeks and demonstrated a total coronary occlusion (TIMI grade 0) in one of the major coronary arteries. CTA was performed using a 64-slice multidetector CT. The presence, and extent of collateralization was assessed by two blinded observers using the Rentrop classification for ICA. CTA accurately identified the presence and location of all 26 total occlusions. The presence of any collaterals was accurately detected in 21/23 patients [sensitivity 91% (CI: 71–98%)] and the absence in three patients [specificity 100% (CI: 29%–100%)]. The sensitivity of coronary CTA to identify patients with collateralization increased from 91 to 94% (CI: 71–99%) and 100% (CI: 59–100%) for collaterals Rentrop grade 2 and 3 in ICA, respectively. Coronary CTA accurately detects the presence of any coronary collateralization in patients with total occlusions. Although CT technology is currently limited in the assessment of individual collaterals and smaller vessels, it may be helpful in the management of patients with total occlusions.     

Chronic total occlusions in peripheral vasculature: techniques and devices

Peripheral artery disease continues to increase in an ever-aging society and consumes a significant part of health resources. Chronic total occlusions account for a significant portion of the lesions encountered by endovascular interventionalists. Unlike the coronary circulation, these occlusions are often long and associated with other features of complexity. The two primary issues concerning these lesions are the ability to safely achieve intimal angiographic success and the long-term durability of therapy. Traditionally, the use of percutaneous techniques was limited to certain anatomic subsets, such as stenosis or total occlusions. However, recent advances in wire technology, re-entry catheters, alternative crossing tools and atherectomy devices have increased the interventional armamentarium for this challenging disease subset. This article will focus on some of the techniques in crossing chronic total occlusions lesions, as well as the available devices to improve long-term patency.     

冠状动脉慢性完全闭塞病变介入治疗完美攻略

冠状动脉慢性完全闭塞病变( chronic total occlusion, CTO)被公认为是冠状动脉介入治疗（percutaneous coronary intervention, PCI）的难点,曾经是PCI的禁忌证。然而PCI医师对CTO的尝试持续超过30年,过去10余年来,得益于导丝通过技术的提高、新器械的使用以及对病理解剖理解的加深,CTO PCI领域取得了巨大进步。CTO成为冠脉介入领域全球性的热点,包括中国在内,越来越多的国家投入或涉足CTO PCI领域。本文就CTO PCI相关策略进行综述。     

First-generation versus second-generation drug-eluting stents in patients with chronic kidney disease: a systematic review and meta-analysis

Background: Chronic kidney disease (CKD) patients are associated with very high rate of adverse cardiovascular outcomes after drug-eluting stents (DES) implantation. The clinical outcomes of second-generation DES versus first-generation DES in CKD patients remain controversial.

Objective: The aim of the current study was to perform a systematic review and meta-analysis to assess the safety and efficacy of second-generation DES versus first-generation DES in CKD patients.

Methods: A systematical search of databases of PubMed, EMBASE, and Cochrane Library was conducted for eligible studies comparing the clinical outcomes of first-generation DES versus second-generation DES. Sirolimus-eluting and paclitaxel-eluting stents were classified as first-generation DES, and everolimus-eluting, zotarolimus-eluting, and biolimus-eluting stent (BES) were classified as second-generation DES. A pooled odds ratio (OR) and 95% confidence interval (CI) were used to summary the estimates. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were also performed.

Results: We identified 14 trials involving 9,542 patients with CKD undergoing percutaneous coronary intervention. First-generation DES implantation was associated with higher risk of long-term all-cause mortality (OR, 1.31; 95% CI, 1.02–1.69; P = 0.04; I² = 0%), in stent restenosis (OR, 1.69; 95% CI, 1.14–2.49; P = 0.008; I² = 49%) and stent thrombosis (OR, 1.64; 95% CI, 1.00–2.69; P = 0.05; I² = 49%) compared with second-generation DES implantation. First-generation DES and second-generation DES showed similar efficacy in decreasing risk of repeat revascularization, myocardial infarction (MI), or major adverse cardiac events (MACE) between first-generation and second-generation DES implantation.

Conclusions: In CKD patients, the use of second-generation DES was associated with lower risk of long-term all-cause mortality, in stent restenosis and stent thrombosis as compared with first-generation DES. No differences were found regarding repeat revascularization, MI, and MACE.     

Expressman锥形延长导管在冠状动脉慢性完全性闭塞病变中的应用

目的 探讨Expressman锥形延长导管在治疗冠状动脉慢性完全性闭塞（chronic total occlusion, CTO）病变中的有效性和安全性。方法 回顾性选择2021年5月至2023年5月复旦大学附属中山医院接受经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）的冠状动脉CTO患者228例，根据使用延长辅助导管类型分为5F Expressman延长导管组（5F组，n＝97）和5-4F Expressman锥形延长导管组（5-4F组，n＝131）。比较两组患者人口学特征、介入操作治疗相关指标及住院期间主要不良心血管事件（major adverse cardiovascular events, MACEs）。结果 两组患者的年龄、性别、吸烟史、PCI史、冠状动脉旁路移植术（coronary artery bypass grafting, CABG）史、既往心肌梗死史比例差异无统计学意义。CTO病变血管中，右冠状动脉比例最高（65.4%），其次是前降支（26.3%）；中位J-CTO评分为3（2，3）分。5-4F组的导管深插长度显著高于5F组[（43.9±18.3）mm vs（29.7±21.3）mm，P＜0.001]。5-4F组术中的压力嵌顿发生率显著低于5F组（3.1% vs 9.3%, P＝0.045），5-4F组的器械通过成功率显著高于5F组（97.7% vs 90.7%, P＝0.019）。两组患者住院期间均未观察到MACEs。结论 5-4F Expressman锥形延长导管在冠脉CTO介入治疗中的应用可提高器械输送成功率，减少压力嵌顿的发生。     

Sirolimus-eluting coronary stents: novel devices for the management of coronary artery disease

Despite major technological advances in the practice of percutaneous coronary intervention, restenosis of the treated arteries remains a challenge for many interventional cardiologists. Sirolimus is a macrolide antibiotic with potent antifungal, immunosuppressive, and antimitotic activities. Sirolimus inhibits in-stent restenosis via 2 major mechanisms of action: by blocking the process of neointimal hyperplasia by inhibiting smooth muscle cell proliferation and by inhibiting inflammatory cell activity. In pivotal clinical trials, the sirolimus-eluting stent has demonstrated significant improvements in angiographic and clinical outcomes compared with bare metal stents in patients with de novo lesions in native coronary arteries. Since the systemic exposure of sirolimus in patients who received the drug-eluting stent is minimal, adverse effects resulting from systemic exposure of sirolimus are unlikely to occur. Further studies are needed to determine the safety and effectiveness of sirolimus-eluting stents in patients with more complex coronary artery lesions. In addition, the long-term safety, efficacy, and cost-effectiveness of this novel drug-eluting device will need to be established in ongoing clinical trials. This review article focuses on the pharmacology as well as clinical studies of the sirolimus-eluting stent.     

单支架及双支架植入治疗冠状动脉分叉病变的临床疗效比较

目的 探讨冠状动脉分叉病变植入单支架或双支架后即刻疗效及对预后的影响.方法 选取88 例冠状动脉分叉病变患者为研究对象,将其分为:单支架植入组:主支植入药物涂层支架,对支架植入术后受影响的分支予球囊扩张;双支架植入组:应用Mini-Crush 技术对主支血管及分支血管分别植入药物涂层支架,比较两组患者支架植入术后即刻血管血流情况、术后6 个月及12 个月心血管事件、术后12 个月冠状动脉造影血管血流情况.结果 46 例患者成功行主支血管支架植入+必要时分支血管球囊扩张,42 例患者成功行双支架植入术,术后即刻造影两组患者主分支血管血流TIMI 3 级、主支血管残余狭窄＞30%差异无统计学意义(P ＞0.05),但双支架植入组术后即刻造影分支血管残余狭窄＞50%患者3 例,单支架植入组13 例(P ＝0.01),住院期间、术后6 个月两组心血管事件差异无统计学意义(P ＞0.05),术后12 个月单支架植入组心血管事件15 例,双支架植入组6 例(P ＝0.044),术后12 个月冠状动脉造影,两组患者主支血管血流TIMI 3 级、主支残余狭窄＞30%差异无统计学意义(P ＞0.05),但双支架植入组术后12 个月分支血管残余狭窄＞50% 7 例,TIMI 血流3 级27 例,单支架植入组分支血管残余狭窄＞50% 18 例,TIMI 血流3 级21 例(P ＜0.05).结论 对冠状动脉分叉病变,行双支架植入术能降低术后即刻、术后12 月分支血管狭窄率,减少术后12 月心血管事件,对冠状动脉分叉病变,双支架植入术优于单支架植入术.