药物洗脱支架时代再狭窄的预防和治疗

药物洗脱支架有效地降低了再狭窄的发生率,扩大了冠脉介入治疗的领域。然而,随着介入治疗的病变越来越复杂,病例越来越多,其本身的再狭窄问题也变得令人瞩目。如何处理药物洗脱支架后的支架内再狭窄,已经成为心脏病学面临的新挑战。本文就药物洗脱支架再狭窄的原因、特点、预测因素、治疗策略作一综述。     

药物洗脱支架的研究进展

经皮腔内冠状动脉形成术及支架置入术已经广泛应用于临床,成为冠心病常规治疗的方法之一,但术后再狭窄的问题一直困扰着广大介入工作者。药物洗脱支架的问世,为解决支架术后再狭窄带来了展新的曙光。本文简要综述药物洗脱支架的应用现状以及新型药物支架的研发进展。     

药物洗脱支架植入后冠脉支架内再狭窄的影响因素分析

目的 探讨药物洗脱支架植入后冠状动脉(冠脉)支架内再狭窄的影响因素.方法 182例置入药物洗脱支架的患者,根据是否发生冠脉支架内再狭窄分为再狭窄组(32例)和未狭窄组(150例).分析冠脉支架内再狭窄的影响因素.结果 再狭窄组与未狭窄组的年龄、体质量指数(BMI)、性别、高血压、饮酒史、肾小球滤过率(eGFR)、糖化血...     

药物洗脱支架在临床的应用

冠心病介入治疗(PCI)用金属普通支架取代球囊扩张,使支架内再狭窄(ISR)近50%下降到20%～30%;药物涂层支架,在防止支架内再狭窄及再次血运重建术(Repeat revasculazation)明显优于金属普通支架.近年药物洗脱支架(DES drug electing stent)问世,使支架内再狭窄率下降至10%以下,成为介入冠心病学发展最快的领域之一,被称为第三个里程碑.我国从2002年开始应用药物洗脱支架,主要有美国强生公司Cypher支架和美国波斯顿公司Taxus支架及国内微创公司的FireBird药物洗脱支架.     

7-Hexanoyltaxol药物洗脱冠脉支架可带来有风险的获益

一项多国研究结果显示，经皮冠脉成形术患者应用大剂量7-Hexanoyltaxol药物洗脱冠脉支架(QuaDDs支架)(Ⅰ)可降低再狭窄率，但是心脏不良事件发生率明显升高。     

再次置入药物洗脱支架治疗经皮冠状动脉支架置入术后早期与晚期支架内再狭窄的对比研究

目的 比较再次置入药物洗脱支架（DES）治疗置入DES后早期（≤1年）与晚期（＞1年）支架内再狭窄（ISR）患者的临床疗效.方法 收集2008年10月至2011年12月在北京安贞医院因DES置入术后ISR接受再次DES置人治疗并完成临床随访的患者资料.根据DES置入术后发生ISR的时间分为早期ISR组和晚期ISR组.对比2组随访期间的主要不良心血管事件（MACE）[包括全因死亡、心肌梗死和靶病变血运重建（TLR）].结果 总计107例患者入选本研究,其中早期ISR组43例,晚期ISR组64例.2组的患者基线资料、靶病变部位、类型、长度、置入支架特征及ISR类型、再次置入支架特征差异均无统计学意义（P＞0.05）.早期ISR组糖尿病患病率明显低于晚期ISR组[22.7％ （10/44）比42.9％ （27/63）,P＜0.01].晚期ISR组MACE发生率明显低于早期ISR组[15.9％ （10/63）比47.7％ （21/44）,P＜0.01];晚期ISR组TLR率明显低于早期ISR组[12.7％ （8/63））比43.2％ （19/44）,P＜0.01].Logistic回归分析显示,DES术后早期ISR（OR=6.47,95％ CI：2.26～18.50,P＜0.01）是DES治疗ISR后再次TLR的唯一预测因素.结论 再次DES置入治疗DES置入后ISR安全有效,但治疗早期ISR时TLR明显升高.     

药物洗脱支架置入治疗冠心病的护理

<正>冠状动脉介入治疗是治疗冠状动脉粥样硬化性心脏病(冠心病)的有效方法。它能迅速增加冠状动脉循环血量,从而缓解心绞痛,使梗死的冠状血管获得更早和更完全的再通,提高了冠心病患者的生活     

Investigation of mass-balance issue in e-beam sterilized paclitaxel eluting coronary stents by SPME/GC-MS

Paclitaxel eluting coronary stents were sterilized by e-beam in a closed system, to investigate sterilization related mass-balance issues and evaluate potential volatile paclitaxel degradation products. A solid-phase microextraction (SPME) method utilizing a polydimethyl-siloxane/divinyl-benzene (PDMS/DVB) fiber was optimized for extracting the volatiles from the head-space of the sterilized stents. GC-MS was used for separation, identification, and quantitation of the components. Benzaldehyde and benzoic acid were identified as paclitaxel related volatile degradation products. Three groups of stents were included in the study, a control group (not exposed to e-beam), a group sterilized at 25 kGy, and a final group sterilized at 75 kGy. The stents sterilized by e-beam at 75 kGy contained significantly higher levels of benzoic acid relative to the controls and the stents at 25 kGy contained intermediate levels of benzoic acid. The benzaldehyde levels increased in the 25 kGy e-beam sterilized stents relative to the control but remained fairly constant in the 75 kGy e-beam sterilized stents relative to the 25 kGy e-beam results. Mechanism for the formation of benzoic acid and benzaldehyde from paclitaxel was proposed. The levels of benzoic acid and benzaldehyde observed on the stents did not resolve the original mass-balance issue, but most likely contribute to the lack of mass balance observed for paclitaxel.     

药物洗脱支架与裸金属支架治疗无保护左主干病变的效果比较

目的：比较药物洗脱支架(DES)和裸金属支架(BMS)在无保护左主干(LMCA)病变中的疗效。方法连续入选了294例无保护LMCA病变患者,其中165例接受DES治疗,129例接受BMS治疗。主要终点是术后5年的主要心脏不良事件(MACE),包括心性死亡、心肌梗死(MI)和靶病变血运重建(TLR)。结果在PSM后的人群中,DES组5年的MACE(P=0.022)、心性死亡(P=0.045)、MI(P=0.049)的发生率均低于BMS组,两组TLR和支架内血栓发生率比较差异无统计学意义(P跃0.05)。 Kaplan-Meier法分析显示,DES组和BMS组的无MACE生存率(80.6%和68.2%,P=0.023)、总体生存率(93.0%和85.3%,P=0.045)、无TLR生存率(84.5%和72.1%,P=0.014)及无MI生存率(89.9%和80.6%,P=0.029)比较差异均有统计学意义。结论在无保护LMCA病变患者中,置入DES组患者的MACE发生率低于BMS组;DES组心性死亡和MI的获益高于BMS组,而TLR的长期获益相当。     

雷帕霉素药物洗脱支架在STEMI合并糖尿病患者急诊PCI中的应用

目的 探讨雷帕霉素药物洗脱支架在急性ST段抬高型心肌梗死（STEMI）合并糖尿病患者急诊经皮冠状动脉介入（PCI）中应用的安全性与有效性.方法 选取本院2010年7月～2013年7月收治的STEMI合并2型糖尿病行雷帕霉素药物洗脱支架置入术患者（79例）作为试验组,选取同期收治的STEMI合并2型糖尿病行金属裸支架置入术患者（43例）作为对照组,对比两组患者术后12个月不良心血管事件发生率及术后即刻、24 h、48 h、72 h血小板聚集情况.结果 试验组患者术后12个月死亡、再梗死、再次靶血管重建等主要不良心血管事件发生率均明显低于对照组,差异有统计学意义（P＜0.05）.两组患者术前即刻、术后即刻及术后24 h血小板聚集情况差异无统计学意义（P＞0.05）,试验组患者术后48、72 h血小板聚集情况明显优于对照组,差异有统计学意义（P＜0.05）.两组患者术后24 h、术后1个月等近期再狭窄发生率差异无统计学意义（P＞0.05）,试验组患者术后6、12个月再狭窄发生率（8.86％、11.39％）明显低于对照组（25.58％、32.56％）,差异有统计学意义（P＜0.05）.结论 STEMI合并糖尿病患者行急诊PCI术后置入支架能在一定程度上改善心肌再灌注情况,且雷帕霉素药物洗脱支架相较于金属裸支架具有更好的远期疗效,其远期不良心血管事件发生率明显偏低,心肌组织水平再灌注情况优势明显,有助于改善患者术后的生活水平.     

Structural identification and characterization of potential degradants of zotarolimus on zotarolimus-coated drug-eluting stents

Identification and characterization of unknown zotarolimus impurities on zotarolimus-coated drug-eluting stents is an important aspect of product development since the presence of impurities can have a significant impact on quality and safety of the drug product. Four zotarolimus degradation products have been characterized by LC/UV/PDA, LC/MS, LC/MS/MS and NMR techniques in this work. Zotarolimus drug substance and zotarolimus-coated stents were subjected to degradation under heat, humidity, acid or base conditions. The HPLC separation was achieved on a Zorbax Eclipse XDB-C8 column using gradient elution and UV detection at 278 nm. All four impurities generated through the degradation were initially analyzed by LC/MS and/or LC/MS/MS for structural information. Then the isolation of these degradants was carried out by semi-preparative HPLC method followed by freeze-drying of the collected fractions. Finally the degradants were studied by ¹H and ¹³C NMR spectrometry. Based on LC/MS, ¹H NMR and ¹³C NMR data, the structures of these impurities were proposed and characterized as zotarolimus ring-opened isomer (1), zotarolimus hydrolysis product, 16-O-desmethyl ring-opened isomer (2) and zotarolimus lower fragment (3). Degradants 1, 2 and 3 have been observed on degraded zotarolimus-coated stent products.     

A validated, stability-indicating HPLC method for the determination of dexamethasone related substances on dexamethasone-coated drug-eluting stents

An HPLC method was developed and validated to determine trace amounts of dexamethasone related substances on dexamethasone-coated drug-eluting stents. Separation of dexamethasone from its major process impurities and degradation products was achieved on a Zorbax Eclipse XDB C8 column using gradient elution and UV detection at 239 nm. The method was validated according to ICH guideline requirements. In addition, stent extraction efficiency, solution stability and method robustness were evaluated. The method was determined to be linear in the range of 0.01-0.30 microg ml(-1) for the quantitation of major dexamethasone related substances. Method accuracy was assessed by spiking dexamethasone acetate at three levels over the range of 0.025-0.175 microg ml(-1). The dexamethasone acetate recovery ranged from 89.6 to 105.8%. The intermediate precision over the three levels was less than 6% (n=9). The method was also shown to be repeatable at concentration levels of 0.025, 0.125 and 0.175 microg ml(-1) dexamethasone with relative standard deviation values of 4.1, 1.7 and 1.6%, respectively. The method was found to be specific, stability-indicating, and sensitive with a detection limit of 0.008 microg ml(-1) and a quantitation limit of 0.025 microg ml(-1) dexamethasone. Finally, the method was demonstrated to be robust, resistant to small variations of chromatographic variables such as pH, mobile phase organic/aqueous composition and column temperature. Identifying unknown dexamethasone degradation products in dexamethasone-coated drug-eluting stents was of critical interest to ensure product quality, since degradants have a significant impact on safety, efficacy, and product storage and handling. The developed chromatographic method was designed to be compatible with mass spectrometric detection. This paper also discusses using this chromatographic method coupled to an ion-trap LCQ mass spectrometer to elucidate proposed structures for four major dexamethasone degradants.     

Decision models for assessing the cost effectiveness of drug-eluting stents

Percutaneous coronary intervention is an increasingly common treatment for many people with coronary disease. Randomised trials using antiproliferative, drug-eluting stents (DES) have shown important reductions in the need for repeat procedures after initial percutaneous coronary intervention. These trials indicate that the growing use of DES has the potential to create major clinical benefits for patients; however, in actual practice, the associated costs may cause financial crises for hospital systems. This paper reviews previously published DES economic decision models from both societal and hospital perspectives. From a social perspective, additional spending for new technologies may be acceptable if these technologies convincingly improve the lives of patients. The models reviewed suggest that DES incurs large costs to both society and hospitals, and currently offers uncertain clinical benefits. More research is recommended to identify high-risk patients who stand to gain significant health benefits from this therapy.     

OCT和IVUS在冠状动脉病变诊断中的对比研究

目的:评价光干涉性断层显像(OCT)在冠状动脉(冠脉)病变中的诊断价值。方法:对7例冠心病患者,在常规冠脉造影后,对病变血管先后行血管内超声(IVUS)和OCT检查,分别测量参考血管和病变血管最狭窄处外弹力膜面积(EMA)、最狭窄处血管管腔面积(LA)、斑块面积(PA)、斑块纤维帽厚度(CD),计算偏心指数(EI)和重构指数(RI),观察斑块类型及斑块夹层和血栓,并比较两者测量指标及对斑块性状判断的差异。结果:7例患者均成功完成了IVUS和OCT检查,术中术后无明显并发症发生。与OCT相比,IVUS高估斑块面积,低估管腔截面积,两者同一部位测得的PA和LA分别是(5.464±0.805)mm2和(4.916±0.952)mm2以及(3.646±0.857)mm2和(4.240±0.976)mm2,差异有统计学意义(均P<0.05);IVUS高估纤维帽厚度,两者同一部位测得的CD分别是(0.206±0.090)mm和(0.146±0.081)mm,差异亦有统计学意义(P<0.05)。OCT发现斑块夹层和血栓有更敏感的趋势。结论:OCT有很高的图像分辨率,在对斑块性状判断上优于IVUS,操作安全可靠。     

急性冠脉综合征患者置入多支架术后应用国产氯吡格雷的疗效观察

目的观察急性冠脉综合征（ACS）患者于多个支架置入术后应用国产氯吡格雷的临床疗效和安全性。方法入选166例本院自2006年10年至2008年3至诊断为ACS行PCI治疗的患者,每个患者置人支架数均I〉2个,所有患者均接受ACS常规治疗,分为两组,分别于术前给予300mg负荷量、术后长期给予每日75mg维持剂量的国产氯吡格雷（泰嘉）和进口氯吡格雷（波立维）,随访术后6个月内,观察主要临床心血管事件和出血事件的发生情况。结果两组患者基线特征、冠脉造影及PCI特征均无明显统计学差异（P〉0．05）;术后随访6个月内两组患者均未出现心源性死亡、恶性心律失常及颅内出血、消化道大出血等严重出血事件,两组患者临床心血管事件比较未见统计学意义。结论ACS患者多支架植入术后应用国产氯吡格雷（泰嘉）进行抗血小板治疗,与同类进口药物波立维相比,在临床有效性及安全性方面的效果肯定,具有较高的效价比。     

Impact of high lipoprotein(a) levels on in‐stent restenosis and long‐term clinical outcomes of angina pectoris patients undergoing percutaneous coronary intervention with drug‐eluting stents in Asian population

Lipoprotein(a) (Lp(a)) is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug‐eluting stents (DES). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DES were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) < 50 mg/dL (n = 485 patients), and Lp(a) ≥ 50 mg/dL (n = 111 patients). The 6–9‐month angiographic outcomes and 3‐year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in the high Lp(a) group and 43 of 550 lesions (7.9%) in the low Lp(a) group (P = 0.001). In multivariate analysis, the reference vessel diameter, low density lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In the Cox proportional hazards regression analysis, Lp(a) > 50 mg/dL was significantly associated with the 3‐year adverse clinical outcomes including any myocardial infarction, revascularization (target lesion revascularization (TLR) and target vessel revascularization (TVR)), TLR‐major adverse cardiac events (MACEs), TVR‐MACE, and All‐MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DES was significantly associated with binary restenosis and 3‐year adverse clinical outcomes in an Asian population.     

阿托伐他汀对急性心肌梗死冠脉介入治疗术后的疗效及再狭窄的影响

目的：观察不同剂量阿托伐他汀对急性心肌梗死（acute myocardial infarction，AMI）冠脉介入治疗（percutaneous coronary intervention，PCI）术后的疗效及再狭窄的影响。方法：选择急性心肌梗死PCI术后的患者162例，按不同剂量阿托伐他汀分为A组20mg／d、B组40mg／d，每组调脂治疗共12个月。分别于PCI术前及PCI术后6个月末、12个月末测定血脂水平、血清C反应蛋白（CRP）、IL-6、NO、降钙素基因相关肽（CGRP）、血浆内皮素-1（ET—1）、肱动脉舒张内径变化率（D％）、肝肾功能及心肌酶水平；主要观察阿托伐他汀疗效、不良反应和心脏不良事件。结果：治疗后B组的TC、低密度脂蛋白胆固醇（LDL-C）、CRP、IL-6、ET-1降低，高密度脂蛋白胆固醇（HDL-C）、NO、CGRP、△D％升高与A组PCI术后同期比较，差异有统计学意义（P〈0．05），并且无严重不良反应。B组降低PCI术后再狭窄的发生率与A组比较，差异也有统计学意义（P〈0．05）。结论：大剂量阿托伐他汀的抗炎作用及改善血管内皮功能明显，能显著降低PCI术后再狭窄的发生率。