药物洗脱支架与支架内再狭窄

随着药物洗脱支架(Drug Eluting Stent, DES)的出现,再狭窄的问题得到进一步的有效控制,目前的临床证据表明DES总的再狭窄率已经在10%以下.但DES的支架内再狭窄ISR仍是临床介入治疗面临的重要问题.     

药物洗脱支架内再狭窄研究的进展

支架内再狭窄(ISR)仍是介入治疗的重点难题。目前ISR机制尚未明确,可能与支架内新生动脉粥样硬化(ISNA)相关,利用血管内超声和光学相干断层成像可进一步评价ISNA性质,从而指导治疗,本文就药物洗脱支架置入术后ISR形成的影响及治疗方面的最新进展作一综述。     

同种和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄有效性的系统评价

目的评价同种药物洗脱支架和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄的有效性。方法计算机检索Pub Med、OVID、Embase、Cochrane图书馆、万方数据库、中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、维普数据库(VIP),收集同种和不同种药物洗脱支架治疗冠状动脉药物洗脱支架内再狭窄的临床资料,共纳入10项研究,1680名患者,使用Rev Man5.2软件进行系统评价。检索时间为各大数据库建库至2015年10月。结果在治疗冠状动脉药物洗脱支架内再狭窄时,采用不同药物洗脱支架可降低靶病变血运重建率(OR=0.73,95%CI为0.55~0.96,P=0.02)和主要不良心血管事件发生率(OR=0.72,95%CI为0.54~0.96,P=0.03)。两组间的病死率(OR=1.03,95%CI为0.49~2.16,P=0.95)和心肌梗死发生率(OR=0.59,95%CI为0.24~1.41,P=0.23)无统计学差异。结论对于药物洗脱支架内再狭窄患者,再次植入不同药物洗脱支架比植入同种支架更获益。     

药物洗脱支架治疗冠状动脉支架内再狭窄和冠状动脉原发病变的随访研究

目的:比较药物洗脱支架(DES)治疗早期(≤1年)、晚期(1年)支架内再狭窄病变(ISR)与冠状动脉原发病变(De novo)患者的长期临床疗效。方法:收集自2008年10月至2011年12月,北京安贞医院因ISR接受DES置入治疗并完成临床随访的患者资料,根据DES术后发生ISR的时间是否1年分为早期ISR组与晚期SR组。选择同期因冠状动脉原发病变(De novo)置入DES治疗的部分患者作为冠状动脉原发病变组(De novo组)。比较三组患者术后1年的主要不良心血管事件[MACE,包括全因死亡、心肌梗死(MI)和靶病变再次血运重建(TLR)]。结果:早期ISR组入选患者80例,晚期ISR组入选患者124例,De novo组入选患者494例。早期ISR组和晚期ISR组糖尿病患病率明显高于De novo组,差异有统计学意义(36.3%vs.41.1%vs.27.1%,P0.01);早期ISR组不稳定型心绞痛比例明显低于晚期ISR组和De novo组,差异有统计学意义(27.5%vs.63.7%vs.70.6%,P0.01);其余基线资料差异无统计学意义(P0.05)。三组在病变部位、病变类型及病变长度方面比较,差异均无统计学意义(P0.05),而早期ISR组与晚期ISR组直径明显小于De novo组,差异有统计学意义[(2.71±0.36)vs.(2.68±0.41)vs.(3.08±0.54)mm,P0.01)]。早期ISR组MACE发生率明显高于晚期ISR组与De novo组(30%vs.15.3%vs.14.2%,P0.01),其中早期ISR组TLR明显高于晚期ISR组与De novo组,差异有统计学意义(26.3%vs.12.1%vs.10.7%,P0.01),而晚期ISR组与De novo组比较差异无统计学意义(15.3%vs.14.2%,P0.05)。结论:DES治疗ISR患者安全有效,但治疗早期ISR组病变TLR发生率高于晚期ISR组及De novo病变。     

冠状动脉药物洗脱支架内再狭窄的最新研究进展

药物洗脱支架（DES）的诞生和不断优化已经大大提高了经皮冠状动脉介入治疗（PCI）的安全性和有效性,但随着病例复杂性的增加和DES的超适应证应用,术后再狭窄率正逐年上升。因此,当前DES时代下,支架内再狭窄（ISR）仍是临床上亟待解决的一大难题。本文将主要就DES置入后ISR发生发展的病理机制、组织病理学及治疗策略的最新研究成果及进展进行综述。     

药物洗脱支架和再狭窄机制的再认识

经皮冠状动脉介入治疗（PCI）是冠心病治疗的一个重要手段,本期杂志刊载了涉及特殊冠状动脉部位介入治疗、电子束CT血流评价再狭窄、炎症因子和血小板聚集功能影响冠状动脉支架置入效果等相关章。PCI已经进入药物洗脱支架（drugeluting stent,DES）时代,我们必须正确看待目前的有关DES的大规模临床研究结果,更清醒认识DES置入后再狭窄的机制、评价再狭窄不同指标的真正临床意义,提高我们的临床研究和治疗水平,进一步改善冠心病的长期疗效。     

冠状动脉药物洗脱支架术后再狭窄研究进展

虽然药物洗脱支架（DES）的临床应用大幅度降低了经皮冠状动脉介入治疗后支架内再狭窄和靶血管再次血运重建的发生率,但是由于越来越多的高危患者和复杂冠脉病变接受介入治疗,因此支架再狭窄的发生率仍高达5％～20％。DES再狭窄的发生机制尚未完全清楚,其处理策略和预防措施还需进一步完善。该文就近年来有关DES再狭窄的研究进展作一介绍。     

药物洗脱支架再狭窄

药物洗脱支架（drug eluting stent,DES）通过在冠状动脉局部持续缓慢释放抗增殖药物来抑制新生内膜形成。与金属裸支架（bare metal stent,BMS）相比,DES再狭窄发生率由20％-30％降至10％以下。     

药物涂层球囊治疗冠状动脉药物洗脱支架内再狭窄临床分析

目的分析药物涂层球囊(DCB)在治疗冠状动脉药物涂层支架内再狭窄病变中的疗效。方法回顾性分析20例冠状动脉药物洗脱支架内再狭窄患者接受药物涂层球囊治疗的临床资料及随访结果。结果 20例患者共21处再狭窄病变接受DCB治疗,术中即刻成功率95.23%,1处病变在应用DCB治疗后并发夹层并出现TIMI 2级血流,然后植入药物洗脱支架(DES)治疗。所有病例术后随访至今无心绞痛再发,未发生主要心血管不良事件。其中12例患者在术后6~9个月接受冠状动脉造影复查,复查时靶病变最小管腔直径与术后即刻直径比较,按病变血管统计,差异无统计学意义(P0.05);合计统计比较差异有统计学意义(P0.05)。结论 DCB治疗DES支架内再狭窄即刻及短期疗效肯定,可以作为支架内再狭窄的一种新的治疗手段。     

药物洗脱支架置入后再狭窄

尽管药物涂层支架较金属裸支架可以明显降低再狭窄率,但随着临床中的广泛应用,药物支架术后亦有10%发生支架内再狭窄,具体机制不明,主要与介入手术操作和涂层药物、支架本身等有关,多发生支架内局限性狭窄,亦有弥漫病变,最佳治疗手段尚存在争议,再次药物支架置入及血管内放射治疗等都是不错的选择。     

莪术组分涂层支架预防猪冠状动脉再狭窄的研究

目的通过中华实验用小型猪冠状动脉再狭窄模型,观察中药莪术组分涂层支架抑制内膜增殖的有效性。方法将18只小型猪随机分为莪术组分涂层支架组(ZES组)、雷帕霉素涂层支架组(SES组)及金属裸支架组(BMS组),每组6只,分别在左前降支、左回旋支及右冠状动脉置入同一种支架各1枚。术后30 d冠状动脉造影后将猪处死,观察支架血管段的病理形态及影像学变化。结果 30 d时,与BMS组比较,ZES组和SES组平均管腔直径和平均管腔面积均明显增大(P<0.05),直径狭窄率和面积狭窄率明显减小(P<0.05);与SES组比较,ZES组和BMS组炎症积分明显降低,内皮化积分明显升高(P<0.05);3组损伤积分比较,差异无统计学意义(P>0.05);光学相干断层扫描及扫描电镜观察,SES支架组30 d时可见部分支架节段内皮化不全及炎性细胞浸润。结论 ZES支架可有效地抑制血管内膜增殖,具有良好的生物相容性。     

Predictors of diffuse-type in-stent restenosis after coronary stent implantation

Diffuse-type in-stent restenosis (ISR) is associated with higher rate of restenosis after balloon angioplasty, requiring new therapeutic modalities; therefore, it is clinically important to identify the determinants of diffuse-type ISR. We evaluate the clinical and angiographic variables to predict diffuse-type ISR after coronary stent placement. Two hundred and ten ISR lesions in 196 patients (diffuse ISR, 114 lesions; focal ISR, 96 lesions) were reviewed in this study. Clinical, procedural and quantitative coronary angiographic parameters were analyzed. Diffuse-type ISR was defined as a ≥50% lumen narrowing and ≥10-mm length. Univariate analysis revealed that initial lesion length, smaller vessel size, diabetes, multivessel disease, multiple stents, and long stent were significantly associated with diffuse-type ISR. However, diabetes was the only independent predictor of diffuse-type ISR by stepwise multiple regression analysis (OR, 3.3; 95% CI, 1.4–7.4, P = 0.001). Diabetes was associated with diffuse-type ISR after coronary stent placement. It may reflect enhanced rate of neointimal hyperplasia within the stent in diabetic patients. Cathet. Cardiovasc. Intervent. 47:406–409, 1999. © 1999 Wiley-Liss, Inc.     

血浆总胆红素浓度与经皮冠状动脉介入治疗后支架内再狭窄的研究

目的探讨冠状动脉粥样硬化性心脏病（冠心病）患者血浆总胆红素（total bilirubin,TBIL）浓度与冠状动脉支架内再狭窄的关系。方法选择241例接受经皮冠状动脉介入（percotaneous coronary intervention,PCI）治疗以及术后1年内再次接受冠状动脉造影（CAG）检查的患者,根据影像结果分为再狭窄组和非再狭窄组,分别在PCI治疗前、出院前及复查冠状动脉造影前测定血浆TBIL浓度。比较分析两组相应的TBIL浓度。结果再狭窄组PCI治疗前、出院前及复查冠状动脉造影前的TBIL浓度与非再狭窄组分别进行比较,差异有统计学意义（P〈0．05）。多因素Logistic回归分析结果显示,血浆TBIL浓度是预测再狭窄的独立危险因子（P〈0．05）。结论血浆TBIL浓度与PCI治疗后再狭窄密切相关．是预测PCI治疗后再狭窄的独立预测因子。     

C反应蛋白水平对冠状动脉支架内再狭窄的预测价值

目的探讨血清C反应蛋白(CRP)与冠状动脉支架内再狭窄(ISR)发生的关系,旨在提高ISR患者临床检出率。方法选择2010年1月~2018年12月首都医科大学附属北京安贞医院急诊危重症中心收治的冠心病首次PCI患者3100例,PCI术后1年复查冠状动脉造影发现ISR患者430例(ISR组),未发现ISR患者2670例(无ISR组),比较2组一般临床资料及实验室化验指标,分析ISR发生的相关因素及与CRP的关系。结果ISR组出院时及随访时CRP水平明显高于无ISR组[17.1(1.1,26.9)mg/L vs 12.9(0.9,23.5)mg/L,P=0.034;15.2(0.7,23.9)mg/L vs 3.9(0.2,7.9)mg/L,P=0.001]。逐步多元回归分析显示,ST段抬高型心肌梗死、出院时及随访时血清CRP水平是预测冠心病支架置入术后ISR的危险因素(P<0.05,P<0.01)。随访时CRP的ROC曲线下面积为0.861(95%CI:0.815~0.907,P<0.01),截点值12.23 mg/L,敏感性80.5%,特异性77.9%;出院时CRP的ROC曲线下面积为0.637(95%CI:0.566~0.709,P<0.01)。结论冠状动脉ISR发生与出院时及随访时CRP水平密切相关,应用随访时CRP水平对ISR进行预测具有较高的敏感性和特异性。     

药物洗脱支架治疗后冠状动脉再狭窄相关因素的分析

目的探讨药物洗脱支架治疗后冠状动脉再狭窄与临床和造影的相关因素。方法入选416例冠状动脉造影(CAG)资料完整的冠心病患者,男性328例,女性88例,共置入支架470枚,按照CAG结果分为再狭窄组59例和无再狭窄组357例,平均造影随访时间(7．91±2．37)个月。结果再狭窄组CAG示61枚支架发生再狭窄(13．0％),女性、既往冠状动脉旁路移植术(CABG)病史、慢性闭塞(CTO)病变病史、最大球囊释放压力、置入支架长度与术后再狭窄相关(P<0．05);置入支架血管直径与再狭窄高度相关(OR=0．61,95％CI:0．43～0．82,P< 0．01)。结论女性、既往CABG病史、CTO病变、血管直径、置入支架长度是支架术后再狭窄的危险因素,而糖尿病史等与再狭窄无关。     

血清补体C1q与经皮冠状动脉药物洗脱支架植入后支架内再狭窄相关性分析

目的目前经皮冠状动脉(冠脉)药物洗脱支架治疗降低了急性冠脉综合征患者的死亡率,然而冠脉支架内再狭窄(ISR)仍是临床中亟待解决的问题。分析支架内再狭窄的相关因素是减少其发生的关键。方法回顾分析于2016年1月至2019年5月于北京安贞医院住院复查冠脉造影的连续病例201例,排除合并感染、支气管哮喘,风湿免疫性疾病、支架植入术后小于12个月的患者(16例),ISR患者(88例,ISR组)以及非ISR患者(97例,非ISR组)纳入研究。比较2组临床特征,血液生化指标差异。受试者工作特征曲线(ROC曲线)及多因素Logistic回归分析血清学指标与支架内再狭窄的相关性。结果ISR组患者血清三酰甘油[(1.55±1.02)vs.(1.23±0.57)mmol/L]、血清小而密低密度脂蛋白[(0.68±0.30)vs.(0.58±0.23)mmol/L]、血清补体C1q[(184.96±37.22)vs.(157.98±20.93)mmol/L]、花生四烯酸介导的血小板聚集率[(11.85±16.79)vs.(6.94±2.53)%]显著高于非ISR组,差异均具有统计学意义。ROC曲线显示血清补体C1q与ISR呈正相关,其诊断ISR的曲线下面积为0.738,P<0.01。以168.95 mg/L为血清补体C1q截点值,其诊断ISR的灵敏度为65.2%,特异度为75%。多因素Logistic回归分析显示,血清补体C1q>168.95 mg/L与ISR呈正相关(OR=4.62,95%CI:2.05~10.40,P<0.01)。结论血清补体C1q水平与经皮冠脉药物洗脱支架内再狭窄密切相关,是支架内再狭窄的诊断因素之一。血清补体C1q是经皮冠脉药物洗脱支架内再狭窄防治的潜在靶点,其在冠脉支架内再狭窄中的作用机制有待进一步研究。     

Reduced incidence of clinical restenosis with newer generation stents, stent oversizing, and high-pressure deployment: single-operator experience

BACKGROUND: Over the last 4 years, several newer generation stents have become available, promising to change the scenery of coronary angioplasty (PTCA) with its attendant restenosis rate. HYPOTHESIS: The aim of this study was to review prospectively the results of a single operator adopting a uniform approach with approximately 0.5 mm stent oversizing and high-pressure (> or = 12-16 bar) deployment and compare them with conventional PTCA in a series of 244 consecutive patients. METHODS: The study included 203 men and 41 women, aged 59 +/- 11 years, who presented with stable angina and/or positive exercise testing (n = 75), unstable angina (n = 161), or acute myocardial infarction (n = 8). Dilated vessels included the left anterior descending artery (n = 139), the right coronary artery (n = 86), the left circumflex artery (n = 47), the ramus branch (n = 4), or venous grafts (n = 2). Stents were implanted for dissection, suboptimal PTCA result, and electively. Two groups were compared: 83 patients who underwent balloon PTCA alone and 161 patients who also received stent(s). RESULTS: The two groups had similar demographics, age (58 +/- 10 vs. 59 +/- 11 years), initial vessel stenosis (92 +/- 7 vs. 93 +/- 6%), and left ventricular ejection fraction (51 +/- 9 vs. 51 +/- 8%). Procedural success was also similar (97.6 vs. 99.4%), but as expected the residual stenosis was much lower in the stent group (< or = 0 vs. 17%). The following stents were employed: J & J (n = 1), NIR (n = 117), ACS (n = 59), AVE (n = 9), Inflow GoldFlex (n = 9), Crossflex (n = 5), Wictor (n = 1), Jostent (n = 16), R stent (n = 9), Seaquence (n = 2) and Wallstent (n = 1). Single stents were used in 118 patients, two stents in 31 patients, three in 6 patients, and four in 6 patients. There was one in-hospital death at 3 days unrelated to the procedure. There were no events of subacute stent thrombosis; all patients in the stent group received combined therapy with aspirin and ticlopidine, the latter for 1 month. During 18 +/- 14 months, the clinical restenosis rate was significantly lower in the stent group (6.9%) than in the PTCA group (28.4%) (p = 0.001). CONCLUSION: In a series of 244 consecutive patients, newer generation stents and a consistent approach of stent oversizing and high-pressure stent deployment by a single operator resulted in high procedural success (99%), lack of stent thrombosis (0%), and a very low clinical restenosis rate (7%).     

Effect of antioxidant probucol for preventing stent restenosis.

Probucol is a lipid-lowering drug that has an antioxidant effect. The authors sought to investigate the effect of probucol on stent restenosis after the usual 3-day pretreatment protocol. From March 1999 to August 2000, 78 patients (mean age, 56 +/- 8; 49 male) with coronary artery disease who underwent coronary stenting were enrolled. After a diagnostic angiography was done, each eligible patient was randomized to either the probucol or the control group. Following the procedure, ticlopidine was administered for 1 month; aspirin and probucol continuously. Angiographic follow-up was done in 81% (57/70) and angiographic restenosis was not different between the two groups (21% vs. 24%; P = 0.81). In conclusion, antioxidant probucol did not show a beneficial effect on stent restenosis with 3 days of premedication protocol.     

Thoracic radiotherapy in patients with lymphoma and restenosis after coronary stent placement.

OBJECTIVES: The aim of this study was to assess the incidence of restenosis after coronary stenting in patients with lymphoma treated with thoracic radiation. BACKGROUND: Patients with Hodgkin lymphoma treated with thoracic radiation have an increased incidence of coronary artery disease (CAD). The incidence of restenosis after percutaneous coronary interventions is completely unknown. METHODS: This study included 12,626 consecutive patients with CAD treated with coronary stenting during a 10-year period. Within this cohort, three subgroups of patients were assessed: patients with lymphoma and previous thoracic radiation (15 patients), patients with lymphoma without thoracic radiation (7 patients) and patients without lymphoma or previous thoracic radiation (control group; 12,604 patients). Coronary stenting was performed after a median [25th; 75th percentiles] of 8 years [4; 17] after thoracic radiation. The primary end point of the study was restenosis at 6-month coronary angiography. RESULTS: Six-month coronary angiography was performed in 14 patients (93%) in the group with lymphoma and radiation, 6 patients (86%) in the group with lymphoma without radiation and 10,032 patients (80%) in the control group (P = 0.38). Angiographic restenosis was found in 12 patients (85.7%) in the group with lymphoma and radiation, 1 patient (16.7%) in the group with lymphoma without radiation and 2,555 patients (25.5%) in the control group (P < 0.001). Multiple logistic regression identified thoracic radiation as an independent predictor of coronary restenosis (odds ratio 21.7, 95% confidence interval, 4.7-100.9, P < 0.001). CONCLUSIONS: Patients with lymphoma treated with thoracic radiation have an increased risk of restenosis after coronary artery stenting.