Clinical development of bivalirudin (Angiox): rationale for thrombin-specific anticoagulation in percutaneous coronary intervention and acute coronary syndromes

As the pathophysiology of acute coronary syndromes (ACS) has been clarified in recent years, major advances have been made in the management of the disease. The magnitude of the thrombotic process triggered upon plaque disruption is modulated by different elements that determine plaque and blood thrombogenicity. Thrombin plays a pivotal role in ACS because of its extensive procoagulant and prothrombotic actions. Antithrombotic therapy and powerful antiplatelet therapies, in addition to early percutaneous coronary intervention (PCI), have become central in the management of ACS. A number of options for anticoagulation regimens are available. However, many agents currently used have significant limitations, recognition of which has led to the development, evaluation and clinical introduction of the class of thrombin-specific anticoagulant agents. This paper will discuss the clinical development of the direct thrombin inhibitor bivalirudin as the core anticoagulant in the contemporary PCI setting and the implications for its use in ACS.     

Bivalirudin: an anticoagulant option for percutaneous coronary intervention

Coronary artery thrombosis is usually triggered by platelet-rich thrombus superimposed on a spontaneously or mechanically disrupted atherosclerotic plaque. Thrombin and platelets both play a role in this process. Unfractionated heparin and aspirin have served as cornerstones in the prevention and treatment of intracoronary thrombus, but unfractionated heparin has several limitations that necessitate the use of adjunctive therapies, such as glycoprotein IIb/IIIa receptor inhibitors and clopidogrel, in order to reduce the risk of ischemic events. These combination therapies, however, typically increase the risk for bleeding complications, as well as the cost and complexity of treatment. Bivalirudin (Angiomax, The Medicines Company), a thrombin-specific anticoagulant, does not share heparin's limitations. Bivalirudin appears to provide clinical advantages over unfractionated heparin therapy in acute coronary syndrome patients and those undergoing percutaneous coronary intervention, without increasing cost or complexity of treatment for most patients.     

Bivalirudin: a review of the pharmacology and clinical application

Among the current agents in the class of direct thrombin inhibitors, bivalirudin (Angiomax^®, The Medicines Company, NJ, USA) has seen increased use in cardiovascular medicine over the past decade through its primary indication as an anticoagulant used during percutaneous coronary interventions. Bivalirudin has been further investigated and used as the anticoagulation strategy in the setting of cardiac and endovascular surgical procedures and is frequently utilized in the management of patients with heparin-induced thrombocytopenia. In comparison with heparin, bivalirudin exhibits a low immunogenic profile and provides similar or reduced major bleeding rates as well as a predictable degree of anticoagulation that is dose related. Bivalirudin primarily undergoes dual elimination via proteolytic cleavage and renal elimination, and requires dose adjustment in the setting of severe renal dysfunction. Given the body of supportive data, bivalirudin is likely to continue to figure prominently as a reliable and efficient anticoagulation strategy. Additional agents in the class of direct thrombin inhibitors are under investigation and may find increasing clinical use.     

经皮冠状动脉介入术治疗急性冠脉综合征综合评价指标的构建

目的:构建急性冠脉综合征(acute coronary syndrome,ACS)患者接受经皮冠状动脉(冠脉)介入术(percutaneous coronary intervention,PCI)的效果评价指标及综合效果指数.方法:应用德尔菲法结合综合指数法确定评价PCI对ACS疗效的指标及权重.结果:经2轮德尔菲专家...     

评分对高龄急性冠状动脉综合征患者介入治疗预后的评估价值

目的：评价Barthel评分应用于高龄急性冠状动脉综合征患者冠脉介入治疗的意义。方法：选择181例75岁以上因急性冠状动脉综合征行冠脉介入治疗的患者。根据Barthel评分,将其分成3组：＜70分组（n=62）、≥70～90分组（n=72）及≥90分组（n=47）。比较3组患者住院后1个月内的临床转归。结果：与≥90分组相比,＜70分组患者年龄较大、女性比例更高、入院时收缩压较低、白细胞计数更多、既往消化性溃疡比例较低、 ST段抬高型心肌梗死比例更高、进行急诊介入治疗的比例更高,差异均有统计学意义（P<0.05)。与≥90分组相比,＜70分组术后左心室射血分数较低、脑钠肽前体（pro- BNP）水平更高、消化道出血比例更高、住院时间更长,差异均有统计学意义（P<0.05)。≥70~90分组和≥90分组上述指标差异均无统计学意义。结论：罹患急性冠状动脉综合征且Barthel评分小于70分的高龄患者住院后1个月内临床转归不佳;这类患者进行冠脉介入治疗时,应慎重权衡风险与获益。     

Prasugrel in acute coronary syndrome patients undergoing percutaneous coronary intervention

Currently, dual antiplatelet therapy with aspirin and clopidogrel represents the key treatment strategy for the prevention of ischemic events in patients with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). However, there is a broad inter-individual response variability to such treatment strategy, and a considerable number of patients persist with inadequate platelet inhibition, which has been associated with an increased risk of ischemic events. Overall, these findings underscore the need for novel antiplatelet agents able to achieve greater platelet inhibition; this can potentially reduce ischemic event rates. Prasugrel (CS-747; LY 640315), a novel third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y₁₂ receptor. Laboratory studies have shown prasugrel to be associated with more prompt, potent and predictable degrees of platelet inhibition compared with clopidogrel. In a large-scale clinical study, which was comprised of high-risk ACS patients undergoing PCI, prasugrel was shown to significantly reduce the short- and long-term risk of ischemic events, including stent thrombosis. However, such significant reduction in ischemic events occurred at the expense of a higher risk of bleeding. Recent clinical trial data analyses have led to a better understanding of the efficacy and safety of prasugrel. This article reviews the currently available data regarding the efficacy and safety of prasugrel in ACS patients.     

临床路径在经皮冠状动脉介入治疗中的应用

目的探讨临床路径在经皮冠状动脉介入(PCI)治疗中的应用效果。方法将126例PCI患者随机分为实验组和对照组各63例。对照组患者采用PCI常规治疗护理方法,实验组患者采用临床路径方法进行治疗护理,即根据PCI患者病情制订临床护理路径图,由经过统一培训的责任护士从入院到出院全程负责,有计划、有组织地对患者实施治疗及健康指导和护理。结果与对照组比较,实验组的平均住院天数及费用明显减少,患者对护理工作的满意度及健康知识掌握率明显提高(均P<0.05)。结论应用临床路径对PCI患者实施治疗护理,可提高临床治疗护理质量,提高护理人员的健康教育技巧,激励患者参与治疗的积极性,而且可缩短平均住院日,减少医疗费用,增加患者满意度,缓解医护人员与患者的关系。     

ACS患者PCI手术预后影响因素的多因素分析

目的：探讨影响急性冠状动脉综合征（ACS）患者经皮冠状动脉介入治疗（PCI）手术预后的相关影响因素。方法连续收集2008年1月至2010年12月在重庆市巴南区人民医院心内科成功行PCI手术的ACS患者114例,随访至2015年12月,分析患者的临床资料;运用Kaplan-Meier法计算ACS患者PCI术后生存率,采用Log-rank法比较PCI手术患者不同临床特征与预后之间的关系,并采用多因素Cox回归分析筛选影响患者预后的独立危险因素。结果全部患者随访11～57个月,中位随访时间26个月;随访期间21例（18．4％）患者发生终点事件,其中一级终点事件死亡6例（5．3％）,二级终点事件复发15例（13．2％）。患者术后生存时间4～57个月,平均生存时间44．5个月,1年、2年、3年生存率（OS ）分别为85．4％、77．7％、72．6％。ACS患者PCI术预后的多因素分析显示,高血压、术后服用阿司匹林服药时间不足一年、术后服用氯吡格雷时间不足一年、术后未服用β-受体阻滞剂是影响PCI手术患者预后（发生终点事件）的独立危险因素（P＜0．05）。结论控制血压、加强PCI手术患者的长期药物治疗对ACS患者PCI术后的预后具有很重要的临床意义。     

冠脉介入对冠心病患者血流及炎症因子的影响

目的观察和分析经皮冠状动脉介入(PCI)干预后冠状动脉血流及基质金属蛋白酶-9(MMP-9)、白细胞介素-6(IL-6)等炎症因子水平的变化。方法选取46例择期行PCI术的急性冠脉综合征(ACS)患者作为PCI组,选取22例行常规冠状动脉造影检查的患者作为CA组,对两组患者术前、术后外周血标本中以及PCI患者术中病变局部血标本中的MMP-9、IL-6水平和术后冠状动脉的校正的TIMI计帧数(c TFC)进行检测和比较。结果 PCI组患者使用造影剂量和术后c TFC均显著高于CA组(P0.05);PCI组患者术后外周血标本IL-6水平较术前显著升高(P0.05)且显著高于CA组(P0.05),PCI组患者术中病变局部血标本IL-6水平显著高于术前或术后的外周血标本(P0.05);PCI组患者的术中病变局部血标本的IL-6水平(r=0.589)、术中局部血标本与术前外周血标本MMP-9水平的差值(r=0.372)和术中局部血标本与术前外周血标本IL-6水平的差值(r=0.628)与患者的c TFC呈正相关(P0.05)。结论 PCI术可显著改善ACS患者的冠脉血流,局部PCI操作、血流再灌注等因素可引起病变局部血清炎症因子水平的上升,其变化幅度较外周血更加显著。     

冠状动脉慢性完全闭塞病变介入治疗临床疗效分析

目的:探讨国人冠状动脉慢性完全闭塞病变(CTO)患者的介入治疗特点及影响因素。方法:入选2017年中国冠状动脉慢性闭塞病变俱乐部(CTOCC)的CTO患者40例,分析介入治疗过程的特点以及操作成功率。结果:40例患者闭塞时间为3~56个月,均为首次介入治疗失败者,J-CTO评分均≥3分,术前均行冠状动脉CT检查,双侧造影使用率为100%。通过前向技术成功开通血管23例,血管内超声(IVUS)指导下正向钢丝技术及平行导引钢丝技术为术者最常采用的正向技术,其中5例患者采用正向内膜下重回真腔(antegrade dissection reentry,ADR)技术4例获得成功;逆向导丝通过法成功完成介入治疗14例,使用Reverse CART技术10例。术中使用平均钢丝数为5.07根,术者最常用软导丝是Sion系列钢丝35例(82.5%),其次为Runthrough钢丝22例(55%),再次为锥形导丝Fielder系列钢丝15例(37.5%),成功通过病变5例(12.5%)。使用硬导引钢丝通过病变32例(80%),通过CTO病变术者最常使用的硬导引钢丝为Gaia系列钢丝23例(57.5%),其次为Conquest系列导引钢丝19例(47.5%),再者为Pilot系列钢丝18例(45.0%)。术中微导管使用率为100%,其中Cosair导管最常使用(33例,82.5%)。操作中IVUS使用22例(55%),主要用于判断导丝远端是否位于真腔、植入支架时管腔直径判断及寻找闭塞血管入口。40例患者平均球囊使用3.24个,平均植入支架2.53个,均为药物洗脱支架,PCI成功37例,未成功3例,PCI成功率达92.5%。住院期间无主要心血管不良事件发生。结论:2017年CTOCC病例介入治疗成功率高于目前国内外CTO介入治疗的平均成功率;这得益于术者经验丰富、术前充分阅片、冠脉CT使用率高、术中IVUS充分使用以及合理的使用导丝、器械及合理的策略选择。     

冠状动脉介入治疗后痉挛的原因分析及护理对策

回顾分析了2003年1月-2005年1月行冠状动脉支架植入术后4例发生冠状动脉痉挛的原因,认为可能与血管的狭窄、术中造影剂或机械刺激、精神紧张等因素有关。针对冠状动脉支架植入术后发生冠状动脉痉挛的时间和规律,认真做好术前评估,尤其是高危患健康教育和心理护理,术后严格床头交接班,了解介入治疗血管及未治疗血管狭窄的情况．并对患发作冠状动脉痉挛时的心电图变化进行分析,加强围手术期的病情观察。     

经皮冠状动脉介入治疗中达肝素钠的安全性与有效性研究

目的 探讨冠心病患者择期行经皮冠状动脉介入治疗(PCI)时应用达肝素钠的有效性与安全性.方法 本试验为前瞻、开放、多中心的研究,从2007年1月至2010年4月共入选拟择期行PCI治疗的患者212例.进导管室前患者没有接受任何抗凝治疗,介入操作前5分钟给予达肝素钠60 U/kg静脉注射;进入导管室前已接受达肝素钠皮下注射治疗(至少48小时)者,末次皮下注射达肝素钠8小时内行介入操作时则不再补充抗凝药物,如果距末次皮下注射达肝素钠8～12小时则补充达肝素钠60 U/kg.术后随访5周.主要疗效指标为死亡、非致命性心肌梗死及因缺血导致的紧急血运重建术的发生率,主要安全性指标为与冠状动脉旁路移植术无关的出血的发生率.结果 入选的212例患者中有78例接受了支架植入治疗,1例患者在植入支架时出现急性支架内血栓形成,经处理未导致急性心肌梗死.2例患者术中见鞘管血栓形成.住院期间有9例(4.2%)患者出现股动脉穿刺部位血肿,程度均较轻,没有引起血红蛋白浓度降低及血流动力学不稳,按TIMI分级属轻度出血.住院期间及术后35天随访期无患者出现死亡、心肌梗死及紧急血运重建.结论 达肝素钠有可能取代普通肝素安全有效地应用于冠心病患者的择期PCI中.     

分层应变评估急性冠状动脉综合征患者经皮冠状动脉介入术后心肌功能

目的观察纵向分层应变评估急性冠状动脉综合征(ACS)患者经皮冠状动脉介入(PCI)术后左心室心肌功能的临床价值。方法收集25例成功接受PCI的ACS患者(PCI组)及25名健康志愿者(对照组)。应用M型、双平面Simpson法、组织多普勒及室壁分层应变分别评价2组左心功能及左心室壁3层心肌运动。结果 PCI组左心室壁各层纵向应变及整体纵向应变由心内膜向心外膜逐渐降低,且均低于对照组(P均<0.05)。2组心内膜与心外膜间整体纵向应变均存在一定跨壁梯度(△GLS),但PCI组△GLS绝对值低于对照组(P<0.05)。结论 PCI术后ACS患者左心室壁纵向应变从心内膜向心外膜逐渐减低;纵向分层应变是评价PCI术后ACS患者心肌和左心功能受损的敏感方法。     

Prognostic value of systemic inflammatory response index in patients with acute coronary syndrome undergoing percutaneous coronary intervention

BackgroundThe systemic inflammatory response index (SIRI) is a novel inflammatory biomarker in many diseases.ObjectivesThe aim of this study was to examine the association between SIRI and adverse events in patients with the acute coronary syndrome (ACS) undergoing percutaneous coronary intervention.MethodsA total of 1724 patients with ACS enrolled from June 2016 to November 2017 at a single centre were included in this study, and SIRI was calculated for each patient. The primary endpoint was the composite of major adverse cardiovascular events (MACE), including overall death, non-fatal myocardial infarction, non-fatal stroke, and unplanned repeat revascularization.ResultsDuring a median follow-up of 927 days, 355 patients had MACE. Multivariate Cox analysis showed that SIRI was significantly associated with MACE (hazard ratio: 1.127, 95% confidence interval: 1.034–1.229 p = .007). The results were consistent in multiple sensitivity analyses. The addition of SIRI had an incremental effect on the predictive ability of the Global Registry of Acute Coronary Events risk score for MACE (integrated discrimination improvement: 0.007, p = .040; net reclassification improvement: 0.175, p = .020; likelihood ratio test: p < .001). The restricted cubic spline showed a monotonic increase with a greater SIRI value for MACE (p < .001).ConclusionSIRI was an independent risk factor for MACE and provided incremental prognostic information in patients with ACS undergoing percutaneous coronary intervention.

KEY MESSAGES

• The SIRI is a strong and independent risk factor for adverse outcomes in patients with ACS undergoing percutaneous coronary intervention.
• Higher SIRI is associated with a more severe disease status.
• The SIRI could increase the prognostic value of the GRACE risk score.

     

阿托伐他汀对急性冠脉综合征行PCI术后疗效及炎症因子的影响

目的探讨两种常规剂量阿托伐他汀对急性冠脉综合征(ACS)行经皮冠状动脉介入术(PCI)患者的疗效及炎症因子的影响。方法行PCI术的ACS患者102例随机分为A组(阿托伐他汀钙10 mg)和B组(阿托伐他汀钙20 mg)。比较2组患者PCI手术前后血脂[总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)]和炎症因子[超敏C反应蛋白(hsCRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]水平,观察术后30、180 d的主要心脏不良事件发生情况。结果 PCI术后,2组TC、TG、LDL-C与术前比较,差异均有统计学意义(P0.05)。2组术前、术后24 h血清TNF-α、IL-6、hs-CRP比较,差异均无统计学意义(P0.05);术后7、30 d比较,差异均有统计学意义(P0.05)。2组主要心脏不良事件发生率比较无显著差异(P0.05)。结论两种剂量的阿托伐他汀治疗ACS患者行PCI均安全有效,均能明显降低术后炎症因子水平。     

老年冠心病患者冠状动脉介入治疗术的临床评价

目的 评估本院75岁以上冠心病患者接受冠状动脉介入治疗术(PCI)的安全性和临床疗效.方法 对医院自2007年12月至2010年8月共60例年龄≥75岁的冠心病患者临床特点、冠脉病变特点、PCI成功率、手术并发症进行回顾性分析,并与94例<75岁患者作比较.结果 ≥75岁老年组患者中,陈旧性心肌梗死、左心功能减退及肾功能减退的比例均明显高于<75岁年龄组,两组比较,差异有统计学意义(χ2分别=4.14、10.75、4.47,P均＜0.05);≥75岁老年组患者的冠脉病变多为多支病变,病变类型多为复杂病变,和<75岁年龄组比较,差异均有统计学意义(χ2分别=3.95、4.52,P均＜0.05);成功置入支架的比例比较,≥75岁老年组明显低于<75岁年龄组,分别为88.33%与96.81%,两者的差异有统计学意义(χ2=4.25,P＜0.05); PCI术中术后发生的并发症比例,≥75岁老年组13.33%,而<75岁年龄组4.25%两者比较,差异有统计学意义(χ2=4.25,P＜0.05);高龄组中住院期间总死亡率10.00%.非高龄组总死亡率1.06%,两组比较,差异有统计学意义 (χ2=4.84,P＜0.05).结论 高龄因素对冠心病患者选择性冠状动脉介入治疗术成功率和安全性有明显的影响.     

经皮冠状动脉介入治疗术中并发症的监测及护理

总结了经皮冠状动脉介入治疗术中出现常见并发症的26例(38例次)患的抢救护理经验。术巾并发症包括心率减慢11例次、低血压15例次、室性心律失常10例次、急性冠脉闭塞2例次。认为术前做好充分准备,术中严密监测心电图、心率、心律和血压．发现异常及时处理,能提高介入治疗的成功率。本组常见并发症抢救成功率为97％。     

冠状动脉介入治疗并发冠状动脉穿孔患者的护理

总结5例冠状动脉介入治疗（PCI）并发冠状动脉穿孔患者的护理经验。除加强PCI常规护理外,重点强调了血液动力学以及心肌损伤标志物和心电图变化的监测。本组3例患者并发急性心包填塞,其中2例为术后迟发性心包填塞;3例并发急性非Q波性心肌梗死,其中1例出现心力衰竭。5例患者经积极处理,未发生Q波性心肌梗死、需紧急冠状动脉搭桥或死亡。冠状动脉穿孔是冠状动脉介入治疗少见而严重的并发症,加强术后护理对及时发现和处理各种并发症、减少不良心脏事件发生至关重要。     

Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment

Objective We investigated how does troponin level (TnT) affect the benefit achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with a high loading dose of clopidogrel. Methods The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included 2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT level (n = 973). The primary end point of the trial was the composite of death, myocardial infarction and urgent reintervention at 30 days. Results In patients with elevated TnT level the incidence of the primary end point was 13.1% in the abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95% confidence interval (CI), 0.52–0.95, P = 0.02]. The combined incidence of death or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the placebo group (RR: 0.71; 95% CI, 0.52–0.96, P = 0.03). In contrast, the incidence of the primary end point in patients with no elevated TnT level was identical in both treatment groups (4.6%). The risk of bleeding was not related to TnT level. Conclusions Baseline troponin level affects the benefit of abciximab in patients with ACS undergoing PCI after pretreatment with a high loading dose of clopidogrel. Abciximab reduces the risk of ischemic events only in patients with ACS and elevated troponin level.