Predictors of Restenosis After Coronary Stent Implantation

Objectives. We sought to determine predictors of restenosis after coronary stenting (CS) in a consecutive series of patients.Background. Although stenting in highly selected patient groups reduces restenosis, the results of stenting in a heterogeneous patient group and the effects of clinical and procedural factors on stent restenosis are currently unclear.Methods. We analyzed the 6-month angiographic outcome of 500 lesions in 463 consecutive patients undergoing successful CS. Clinical, qualitative and quantitative angiographic variables were correlated with restenosis assessed as both a binary and a continuous variable.Results. Restenosis, defined as the presence of >50% diameter stenosis in the dilated segment, was present in 105 (26%) of the 405 lesions with angiographic follow-up. The mean late lumen loss during the follow-up period was 0.79 ± 0.64 mm. Implantation of multiple stents (p < 0.0001) and a high acute gain (p < 0.0002) were independently associated with a higher late lumen loss. In contrast, the use of high inflation pressure (p < 0.02) and Palmaz-Schatz stents (p < 0.005) was independently associated with a lower late lumen loss. When restenosis was defined as a qualitative variable, implantation of multiple stents (p < 0.001), stenosis length (p < 0.01), small reference diameter (p < 0.02) and stent type other than Palmaz-Schatz (p < 0.01) were independent predictors of restenosis. None of the clinical variables tested was associated with restenosis.Conclusions. Coronary stenting in an unselected patient group is associated with an acceptable restenosis rate. Although some risk factors were identified, the risk of restenosis was not related to most of the variables tested. This suggests that the superiority of CS over balloon angioplasty, in terms of restenosis, might also apply to subgroups of patients that were not included in the recent randomized studies.     

Successful Coronary Stent Implantation Using Local Nitric Oxide Donor Delivery

With the introduction of high pressure balloon inflations and antiplatelet therapy, the incidence of stent thrombosis has been markedly reduced, but the incidence of late stent restenosis has not. A new strategy may be local drug delivery, which maintains sustained local concentration and limits systemic complications. To evaluate the efficacy of local nitric oxide (NO) donor delivery on stent thrombosis and complications, local NO donor delivery was performed in stented patients. NO donor (2.0-mg molsidomine) was delivered (1.0 mL/min > 10 min) using the Dispatch Catheter after predilation of target lesions in 13 patients (6 angina, 7 myocardial infarction, age 53.1 ± 11.4 years). After local NO donor delivery, Palmaz-Schutz stents were placed using standard methods. Follow-up coronary angiograms were performed 48 hours and 6 months after stenting. None of the patients had hypotensive effects, ischemic symptoms, or ECG changes during and after local NO donor delivery. APTT and CK values were unchanged at 3 and 24 hours after local NO donor delivery and stenting. Follow-up coronary angiograms at 48 hours and 6 months showed all stents patent with TIMI III flow and without intrastent thrombus. No target lesion revascularization and 100% event-free survival were observed during the 6-month clinical follow-up period. Intracoronary stenting may be performed safely and effectively by local NO donor delivery prior to stent implantation.     

冠状动脉支架术后再狭窄的危险因子

冠心病危险因素、血管造影下冠状动脉病变特征、支架术操作技术参数是影响冠脉病变支架术后再狭窄的主要危险因子。这些危险因子主要有糖尿病、冠脉病变长度、病变狭窄程度、病变类型,以及支架长度、支架类型等,这些危险因子在不同基础疾病和冠脉病变条件下对支架术后再狭窄的影响作用不同。     

Drug-Coated Balloon Angioplasty Versus Drug-Eluting Stent Implantation in Patients With Coronary Stent Restenosis

BackgroundIn patients with coronary in-stent restenosis (ISR) requiring reintervention, it is unclear if the choice of treatment should depend on whether the restenotic stent was a bare-metal stent (BMS) or a drug-eluting stent (DES).ObjectivesThis study aimed to assess the comparative efficacy and safety of the 2 most frequently used treatments — angioplasty with drug-coated balloon (DCB) and repeat stenting DES — in patients with BMS-and DES-ISR.MethodsThe DAEDALUS (Difference in Antirestenotic Effectiveness of Drug-Eluting Stent and Drug-Coated Balloon Angioplasty for the Occurrence of Coronary In-Stent Restenosis) study was a pooled analysis of individual patient data from all 10 existing randomized clinical trials comparing DCB angioplasty with repeat DES implantation for the treatment of coronary ISR. In this pre-specified analysis, patients were stratified according to BMS- versus DES-ISR and treatment assigned. The primary efficacy endpoint was target lesion revascularization (TLR) at 3 years. The primary safety endpoint was a composite of all-cause death, myocardial infarction, or target lesion thrombosis at 3 years. Primary analysis was performed by mixed-effects Cox models accounting for the trial of origin. Secondary analyses included nonparsimonious multivariable adjustment accounting also for multiple lesions per patient and 2-stage analyses.ResultsA total of 710 patients with BMS-ISR (722 lesions) and 1,248 with DES-ISR (1,377 lesions) were included. In patients with BMS-ISR, no significant difference between treatments was observed in terms of primary efficacy (9.2% vs. 10.2%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.51 to 1.37) and safety endpoints (8.7% vs. 7.5%; HR: 1.13; 95% CI: 0.65 to 1.96); results of secondary analyses were consistent. In patients with DES-ISR, the risk of the primary efficacy endpoint was higher with DCB angioplasty than with repeat DES implantation (20.3% vs. 13.4%; HR: 1.58; 95% CI: 1.16 to 2.13), whereas the risk of the primary safety endpoint was numerically lower (9.5% vs. 13.3%; HR: 0.69; 95% CI: 0.47 to 1.00); results of secondary analyses were consistent. Regardless of the treatment used, the risk of TLR was lower in BMS- versus DES-ISR (9.7% vs. 17.0%; HR: 0.56; 95% CI: 0.42 to 0.74), whereas safety was not significantly different between ISR types.ConclusionsAt 3-year follow-up, DCB angioplasty and repeat stenting with DES are similarly effective and safe in the treatment of BMS-ISR, whereas DCB angioplasty is significantly less effective than repeat DES implantation in the treatment DES-ISR, and associated with a nonsignificant reduction in the primary composite safety endpoint. Overall, DES-ISR is associated with higher rates of treatment failure and similar safety compared with BMS-ISR.     

冠心病药物洗脱支架植入患者介入前后中医证型变化的研究

目的探讨冠心病患者药物洗脱支架植入前后中医证型变化的规律及药物支架对中医证型的影响。方法对108例冠心病患者行药物洗脱支架植入术前后进行中医证候分型,常见有气虚、阳虚、阴虚、气滞、血瘀、痰浊等证型。按术前、术后24h、术后1周、术后1个月4个时间段进行统计分析。结果标实证中除痰浊外,气滞证在介入术后24h、术后1周、术后1个月各阶段比较有统计学意义(P0.05),各阶段与术前比较有统计学意义(P0.01);血瘀证除术后24h与术后1周比较无统计学意义(P0.05)外,余各组间比较有统计学意义(P0.01);在本虚证中气虚、阳虚、阴虚各证各阶段比较无统计学意义(P0.05)。结论药物洗脱支架介入治疗明显改善冠心病气滞证和血瘀证,充分证明了气滞血瘀是介入术后再狭窄的病机关键;但对本虚证的改变无统计学意义,故不能从根本上改变冠心病的本虚标实的病机特点。     

冠状动脉药物涂层支架后再狭窄与炎症反应的相关性

药物涂层支架的应用使冠心病的介入治疗有了长足进展,但是支架再狭窄仍是不容忽视的问题。现就支架后的炎症反应和再狭窄的关系,药物涂层支架对于抑制炎症和降低再狭窄发生率的作用机理进行综述。     

Long-Term Restenosis After Multiple Stent Implantation: A Quantitative Angiographic Study

Elective high pressure stent implantation in focal coronary lesions has a high procedural success and low incidence of restenosis in comparison with balloon angioplasty. For the treatment of diffusely diseased coronary arteries, however, a high incidence of subacute thrombosis and late restenosis has been reported. The aim of this study was the prospective evaluation of procedural and long-term outcome after implantation of multiple stents. In a consecutive series of 48 patients, 48 lesions were treated with the implantation of 120 stents (2.5 ± 1.0 stents/lesion). Stent implantation was performed electively in 15%, for dissection in 56%, and for suboptimal balloon angioplasty result in 29% of patients. The lesion length before stenting, including balloon angioplasty induced dissections, was 28.5 ± 9.8 mm (range 20–62), the mean length of the stented segment was 40 ± 16 mm. The procedure was successful in 45 patients (95%). Procedural related complications included two urgent bypass operations (4%) and one transmural myocardial infarction (2%). Two subacute stent thrombosis events (4%) occurred, both in-hospital, 1 and 3 days after implantation. Follow-up was obtained in 43 eligible patients at 6.4 ± 1.3 months, revealing an overall restenosis rate of 30% (13 patients). Quantitative angiography (CAAS II, edge detection algorithm) showed a minimal lumen diameter of 0.93 ± 0.28 mm (diameter stenosis 62%± 13%) before treatment, 2.81 ± 0.26 mm (diameter stenosis –4 ± 13%) after stenting, and 1.79 ± 0.58 mm (diameter stenosis 30%± 20%) at follow-up. Predictors of restenosis were not identified. Thus, multiple stent implantation has high procedural success and the late restenosis of long lesions after multiple stents compares favorably with balloon angioplasty.     

血清骨桥蛋白对冠状动脉支架植入术后再狭窄的预测价值

目的探讨经皮冠状动脉介入治疗(PCI)后患者血清骨桥蛋白(OPN)水平对支架内再狭窄(ISR)的预测价值。方法收集我院接受PCI后随访1年、复查冠状动脉造影检查的患者120例,其中男68例,女52例,平均年龄为59.38±11.13岁。根据冠状动脉造影结果分为再狭窄组和无再狭窄组,复查冠状动脉造影时检测两组患者血清OPN等生物化学指标,比较两组临床资料、OPN等生物化学指标水平。结果再狭窄组患者血清OPN水平显著高于无再狭窄组,差异有统计学意义(4.79±1.09μg/L比3.11±1.13μg/L,P0.01)。Logistic多因素回归分析显示,OPN升高是PCI后ISR发生的独立危险因素(OR=3.034,95%CI为1.532~6.007,P0.01)。在OPN预测ISR能力的ROC曲线中,其曲线下面积为0.872,95%CI为0.770~0.975,P0.01;当OPN取4.16μg/L时,其阳性预测价值为56.5%,阴性预测价值为95.9%,敏感性为76.5%,特异性为89.3%,准确性为88.3%。结论 PCI后患者血清OPN水平与ISR密切相关,血清OPN的水平对ISR的发生具有一定的预测价值,尤其是其阴性预测价值高。     

Outpatient Coronary Stent Implantation

Objectives. This study was performed to explore the feasibility of coronary Palmaz-Schatz stent implantation on an outpatient basis.Background. To optimize the applicability of coronary stenting by limiting bleeding complications and length of hospital stay, the transradial approach has been demonstrated to be an effective technique. Immediate ambulation opens the way to outpatient treatment.Methods. Patients selected for Palmaz-Schatz stent implantation received anticoagulation with Coumadin. At an international normalized ratio >2.5, stenting was performed through the radial approach. Starting in December 1994, patients were treated with Ticlopidin. Heparin was administered during the procedure. Suitability for same-day discharge was assessed on the basis of preprocedural, postprocedural and periprocedural criteria. Patients were mobilized after immediate sheath removal, followed by same-day discharge. Follow-up examinations were performed the next day, at 2 weeks and at 1 month after stenting.Results. Of 188 patients who underwent Palmaz-Schatz coronary stent implantation through the radial artery between May 1994 and July 1995, 88 remained in the hospital for various reasons. In the 100 outpatients (Canadian Cardiovascular Society classes III and IV, n = 90 [90%]), 125 stents had been implanted to cover 110 lesions. No cardiac or bleeding events were encountered within 24 h (95% confidence interval 0 to 3.6) of stenting. At 2-week follow-up, one patient was readmitted (day 4) because of a bleeding abdominal aortic aneurysm requiring operation. Two patients were readmitted 2 weeks after discharge, one with subacute thrombosis and one with angina and anemia that was treated with blood transfusions. At 1-month follow-up, no complications were observed.Conclusions. After an optimal transradial Palmaz-Schatz coronary stent result, patients can safely be discharged on the day of treatment.(J Am Coll Cardiol 1997;29:323–7)     

小型猪冠状动脉置入过大直径支架建立再狭窄动物模型

目的：用置入过大直径冠状动脉内支架的方法,在正常小型猪建立模拟人类冠状动脉再狭窄的实验动物模型。　　方法：金属支架由３１６ Ｌ医用不锈钢丝编织而成,将不锈钢支架固定在３．０ ｍ ｍ 经皮冠状动脉腔内成形术（ＰＴＣＡ）球囊上,然后通过８ Ｆ大腔引导导管置入小型猪冠状动脉前降支中段,球囊与血管直径之比为１．１～１．３∶１。　　结果：支架成功置入４只动物冠状动脉前降支中段。在支架置入后３个月重复冠状动脉造影显示：均发生再狭窄,平均管腔直径狭窄为（５５．８０±２３．０６）％ 。组织病理学结果显示：内弹力板撕裂,广泛新生内膜增生及严重管腔狭窄,平均新生内膜厚度和新生内膜面积分别为（１．０９±０．０６ ｍ ｍ ２ 和１．１８±０．３３ ｍ ｍ ２ ）。平均百分狭窄面积为（８６．８０±９．２４）％ 。　　结论：①使用直径过大的球囊扩张型支架可成功地建立再狭窄动物模型。②该模型经济实用,其组织病理学表现与人类再狭窄结果十分相似,并可能有助于检测和评估再狭窄的预防措施     

心肌桥介入治疗后支架内再狭窄及其再次治疗效果的观察

目的观察心肌桥病变介入治疗的再狭窄率及其治疗效果。方法选择有症状的单纯心肌桥改变且收缩期严重狭窄(≥95%)者17例作治疗组(A组),对照组选择单纯前降支动脉粥样硬化严重狭窄(≥70%)者54例(B组),两组均应用普通冠脉支架介入治疗。结果两组介入手术均成功,两组支架植入后的血管内径及支架长度比较无显著差别(P>0.05)。A组6个月内8例(47%)出现再狭窄,B组8例再狭窄(14.8%),A组和B组的再狭窄率有显著差别(P<0.05);两组中再狭窄病人均再次接受治疗。平均随访20月,A组8例中7例未再发生支架内狭窄及心绞痛事件,1例再次支架内狭窄,B组再次介入治疗的6例中1例再次支架内狭窄。结论心肌桥病变的介入治疗远期疗效尚好,但远期支架内再狭窄率较高,需再次介入治疗。     

Sustained Local Delivery of Dexamethasone by a Novel Intravascular Eluting Stent to Prevent Restenosis in the Porcine Coronary Injury Model

Objectives. This study sought to assess the feasibility, safety and efficacy of sustained intracoronary delivery of dexamethasone by a novel polymer-coated eluting stent.Background. Development of techniques to provide sustained local drug delivery has focused on polymers as matrices for drug incorporation and elution.Methods. A tantalum wire stent was coated with dexamethasone (0.8 mg) suspended in a matrix of either low (∼80 kD) or high (∼321 kD) molecular weight poly-l-lactic acid (PLLA [0.4 mg]). Uncoated stents, stents coated with PLLA or stents coated with dexamethasone in PLLA were overexpanded by 30% to the normal vessel diameter in the coronary arteries of juvenile farm pigs. Animals were euthanized 28 days later, and neointimal thicknesses were measured. Additional pigs underwent placement of stents coated with high molecular weight PLLA–dexamethasone for assessment of arterial tissue and serum concentrations of dexamethasone at 1 h and 1, 2, 10 and 28 days after stent implantation.Results. In vitro dexamethasone release occurred over the first 6 days. Stents coated with low molecular weight PLLA produced an intense inflammatory neointimal response. Stents utilizing the high molecular weight PLLA were well tolerated within the coronary vessel during the 28-day experiment. However, dexamethasone did not decrease neointimal hyperplasia. Dexamethasone concentrations in the arterial tissue were ∼300,000-fold higher than those in the serum 24 h after stent implantation, remaining ∼3,000-fold higher at 28 days.Conclusions. The eluting stent utilizing high molecular weight PLLA appeared to be a well tolerated and effective means of providing sustained, site-specific drug delivery to the porcine coronary artery wall for at least 28 days.(J Am Coll Cardiol 1997;29:808–16)     

Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS Study)

OBJECTIVES: This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND: Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS: Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS: Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS: In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.     

冠状动脉支架置入术后抗血小板治疗和出血风险的综合考量

冠状动脉支架置入术后强化抗血小板治疗可预防支架内血栓形成,置入药物洗脱支架的患者,至少双联抗血小板治疗12个月。但长期的双联抗血小板治疗给患者带来获益的同时也增加了出血风险,因此应根据支架内血栓形成危险分层和出血风险进行综合考量,采取个体化的治疗策略,并加强对患者药学监护、用药宣教和随访管理。在治疗过程中及时发现不良事件及潜在问题,并权衡利弊后处理,保障患者长期抗血小板治疗的安全有效。