肝素标准化抗凝方案在急性冠状动脉综合征中的应用

目的:急性冠状动脉综合征(ACS)已经成为威胁人类健康的主要杀手,普通肝素(Unfractionated heparin,UFH)抗凝在ACS的治疗中起着非常重要的作用.尽管UFH应用相当广泛,但目前临床上UFH的应用非常不规范.方法:选择2006年1月至2007年1月在我院住院治疗的ACS患者60例.所有患者均采用静脉UFH抗凝至少24 h,并随机分为A、B 2组.A组为试验组,按预先设定的肝素标准化治疗方案调节剂量;B组为对照组,由值班医生凭经验调整剂量.以活化部分凝血活酶时间(APTT)45～75 s作为UFH抗凝治疗范围.结果:A组和B组分别测量APTT共195和197次,达标比例分别为74.9%(146次)和49.7%(98次),P<0.01;B组中有近一半的病例未达到治疗范围;试验组超出治疗范围的比例高(10.3%),但未见严重出血病例.A组达标所需时间为(2.8±3.2) h、B组为(7.8±3.1) h,P<0.01;24 h内维持在治疗范围内的时间A组(16.3±3.2) h、B组(11.4±4.1) h,P<0.01.结论:UFH标准化治疗方案可以安全有效的应用于ACS患者中,值得大力推广.     

急性冠状动脉综合征介入治疗中应用那屈肝素的临床研究

目的 研究急性冠状动脉综合征患者在经皮冠状动脉介入治疗前应用那屈肝素的合适剂量并评估其安全性.方法 236例急性冠状动脉综合征高危患者随机分为Ⅰ组(那屈肝素0.075ml/10 kg,120例)和Ⅱ组(那屈肝素0.1 ml/10 kg,116例).两组给予相应剂量那屈肝素,每12 h皮下注射1次,至少48 h,最后一次注射1 h后行经皮冠状动脉介入治疗,术中不再追加那屈肝素.分别在末次注射前、注射后1 h、2 h、4 h、6 h、8 h测定血浆抗Xa因子活性.观察记录患者30 d内的主要心脏不良事件(死亡、再梗死、血运重建)及出血事件.结果 两组的一般临床资料、30 d内随访主要心脏事件及出血发生率差异均无统计学意义(P>0.05).各时间点血浆抗Xa因子活性Ⅱ组高于Ⅰ组,差异有统计学意义(P<0.01).结论 在急性冠状动脉综合征介入治疗前应用两种剂量那屈肝素均能达到有效的抗凝效果.     

急性冠状动脉综合征介入治疗前应用依诺肝素有效性和安全性研究

目的　前瞻性的评价无ST段抬高的急性冠状动脉 (冠脉 )综合征患者接受冠脉介入治疗前应用依诺肝素的安全性和有效性。方法　急性冠脉综合征患者入院后给予依诺肝素 1mg/kg ,皮下 ,1 /1 2h ,至少 48h ,在最后一次注射后 8h内行介入检查或治疗。术中 /术后不再追加肝素或低分子肝素。部分病人术后集中测定抗Xa因子活性。结果　 50 7例患者完成了本研究。 1 76例 (93 .2 % )的患者抗Xa因子活性 >0 .5IU/ml。30d内的随访中 ,急性心肌梗死 1 6例 (3 .2 % ) ,再发不稳定性心绞痛 34例 (6 .7% ) ,1例 (0 .2 % )进行了血运重建 ,1例死亡 (十二指肠穿孔 )。轻微出血 2 4例 ,占 4 7%。30d后的随访有 1例发生非Q波心肌梗死 ,1例再发不稳定性心绞痛。结论　高危急性冠脉综合征病人皮下注射依诺肝素至少 48h ,最后一次注射 8h内行介入检查或治疗 ,不再给抗凝制剂 ,对病人安全有效     

老年慢性冠状动脉综合征抗栓治疗患者出血风险评估方法

2019年ESC发布了老年慢性冠状动脉综合征(CCS)诊断和治疗指南,提出对高危的CCS患者可以延长双联抗血小板治疗或进行双通道抗栓治疗[1].随着我国进入老龄化社会,老年CCS比例越来越高.老年患者既有高缺血风险,也有高出血风险.这主要是由老年患者的临床特点所决定,包括多病共存、复杂冠状动脉病变、衰弱、跌倒、营养不良...     

老年急性冠状动脉综合征患者介入术中应用替罗非班的疗效和安全性

目的 探讨老年急性冠状动脉综合征(ACS)患者经皮冠状动脉介入术(PCI)中应用替罗非班的疗效和安全性. 方法 将256例高危ACS患者,随机分为替罗非班组(替罗非班+PCI,130例)和常规PCI组(126例),替罗非班组又根据年龄分为老年组(68例,≥60岁)和非老年组(62例,<60岁)2个亚组.两组患者PCI术后罪犯血管的心肌梗死溶栓治疗(TIMI)3级血流达标率、校正的TIMI帧计数(CTFC)、心肌灌注分级(TMPG),以及36 h和30 d的主要心脏不良事件发生率作为疗效观察指标.并观察两组患者术后血小板减少和出血并发症的发生率. 结果 替罗非班组PCI术后TIMI3级血流发生率较常规PCI组高,但差异无统计学意义(93.6%比91.3%,χ~2=1.02,P=0.313),TMPG 3级所占比例替罗非班组高于PCI组(83.1%比67.5%,χ~2=4.05,P=0.046),CTFC示替罗非班组血流快于PCI组(31.6±7.7比23.8±6.1,t=2.49,P=0.026).两组在36 h和30 d的主要心脏不良事件发生率差异均有统计学意义(6.9%比19.0%,χ~2=6.30,P=0.013;3.8%比11.90%,χ~2=5.82,P=0.018).与常规PCI组比较,替罗非班组TIMI轻度出血的发生率有增加趋势(20.2%比15.2%,χ~2=3.65,P=0.065).亚组分析表明,老年组轻度出血并发症的发生率较非老年组稍增高(25.0%比14.5%,χ~2=4.98,P=0.026),但两组严重出血事件发生率和血小板减少发生率均相似. 结论 老年ACS患者介入术中使用替罗非班是有效和安全的,其疗效优于常规治疗,但轻度出血风险有可能增加.     

低分子肝素在急性冠脉综合征和冠心病介入治疗中的应用

急性冠脉综合征（ACS）和冠心病的介入治疗方案中,抗凝是非常重要的一个环节。近年来,由于低分子肝素（LMWH）不但具有普通肝素的抗凝作用,而且有较高的生物利用度及较好的预期剂量反应,使其在ACS患者中大量应用,而在心导管室中的应用正在临床试验中。LMWH是一种很有前景的药物,用于ACS的治疗无论是在临床效果、安全性还是在方便使用方面,均具有潜在的优势。本文就这方面的进展加以综述。     

低分子肝素在急性冠脉综合征中的应用

急性冠脉综合征(ACS)治疗方案中，抗凝是非常重要的一个环节。与普通肝素相比低分子量肝素在降低ACS患者心脏事件发生方面有更优或至少相同的疗效。本文就低分子肝素在ACS中的应用综述如下。     

急性冠状动脉综合征患者急诊介入治疗临床研究

目的分析本中心急性冠状动脉综合征患者的急诊介入治疗详细特征及趋势,以便更及时、有效地救治患者。方法对在我中心实施急诊介入治疗的230例急性冠状动脉综合征患者进行分析,总结病例的临床特征、介入治疗时间窗、治疗情况及近期预后。结果平均年龄增大、高龄及高危患者增多,治疗时间窗中各时间段(发病→急诊科→导管室→首次球囊扩张)均有缩短,其中导管室→首次球囊扩张时间缩短显著;药物支架、远端保护装置、血栓抽吸器、预防性冠状动脉联合注射防止无复流药物在近两年增长迅速,无血流发生率、主要心血管事件发生率及平均住院日显著下降,同时溶栓后介入治疗较直接介入治疗各种严重出血并发症无明显增加。结论急诊介入治疗是急性冠状动脉综合征的最有效治疗方法之一,各种新型辅助技术的使用可有效预防严重并发症的发生。     

老年急性冠状动脉综合征患者急诊介入治疗中冠状动脉内应用替罗非班的临床观察

目的探讨对于行急诊经皮冠状动脉介入治疗(PCI)的老年急性冠状动脉综合征(ACS)患者,冠状动脉内应用替罗非班的有效性及安全性。方法选择行急诊PCI的老年ACS患者118例,随机分为对照组(静脉内使用替罗非班负荷量)和研究组(冠状动脉内使用替罗非班负荷量),每组各59例患者。比较两组PCI术后即刻冠状动脉造影结果,PCI术后7、30 d时主要不良心血管事件(MACEs)发生率间的差异。结果 PCI结束后共有115例患者入选。研究组(58例)与对照组(57例)比较,患者PCI术后梗死相关血管血栓积分(0.7±0.2比1.6±0.5,P<0.01)、TIMI血流分级(TIMI 3级:51%比41%,P<0.05)及TIMI心肌灌注分级(TMPG 3级:49%比38%,P<0.05)均明显改善,远端血管栓塞的发生率也明显降低(1.7%比14%,P<0.05)。PCI术后30 d时研究组患者的左心室射血分数较对照组明显改善[(67.4±6.2)%比(60.7±4.6)%,P<0.05]。研究组PCI术后7 d时总MACEs的发生率明显低于对照组(3.5%比17.5%,P<0.05),但PCI术后30 d时两组总MACEs的发生率之间比较差异无统计学意义(1.7%比7.0%,P>0.05)。两组患者用药后出血并发症的发生率之间比较差异无统计学意义(P>0.05)。结论对于行急诊PCI的老年ACS患者,与静脉内使用替罗非班相比,冠状动脉内应用安全,且更有利于改善PCI术后冠状动脉血流、心肌灌注,7 d时MACEs发生率低于对照组,30 d时无明显差别。     

直接凝血酶抑制剂在急性冠状动脉综合征中的应用

本文主要介绍几种直接凝血酶抑制剂的功能特点，并与肝素进行比较，着重阐述了直接凝血酶抑制剂在急性冠状动脉综合征中的临床应用及实验研究。资料显示，与肝素相比，直接凝血酶抑制剂与肝素同样有效，甚至效果更佳，其安全性优于肝素。     

低分子肝素治疗高原老年急性冠状动脉综合征患者的临床研究

目的观察低分子肝素治疗高原老年急性冠脉综合征（ACS）患者的疗效及安全性。方法将90例老年ACS患者随机分为常规治疗组（n=42）和延长低分子肝素治疗组（n=48）,常规治疗组采用低分子肝素（依诺肝素）皮下注射治疗5～7d,延长低分子肝素治疗组治疗10～14d,其余基础治疗相同。观察30d内心血管事件、出血事件和血小板减少的发生率。结果常规治疗组30d内心血管事件的发生率为19．0％,延长治疗组为4．2％,两组间差异有统计学意义（P〈0．05）;常规治疗组30d内出血事件的发生率为4．8％,延长治疗组为6．3％,两组间差异无统计学意义（P〉0．05）;两组患者中均未观察到血小板减少的发生。结论延长使用（10～14d）低分子肝素治疗高原老年ACS可显著降低30d内心血管事件的发生率,且不增加出血风险和血小板减少事件的发生率。     

老年非ST段抬高急性冠状动脉综合征患者早期PCI的临床疗效分析

目的 评价老年非ST段抬高急性冠状动脉综合征(ACS)患者早期行经皮冠状动脉介入治疗(PCI)的临床疗效.方法 对58例发病在48 h以内的老年非ST段抬高ACS患者早期行PCI.观察患者术后主要不良心血管事件(包括再次心肌梗死、靶血管再次血管重建和死亡)的发生情况.结果 冠状动脉造影(CAG)显示2支或2支以上血管病变的患者占74.14%,B型和C型病变占89.66%.58例患者共干预病变血管76支,靶病变87处,置入支架96个.56例患者手术成功,手术成功率96.55%(56/58).对55例患者术后随访6～14个月,无心肌梗死和死亡发生.6例(10.91%)患者术后4～10个月复发心绞痛,5例行CAG复查,发现2例支架再狭窄和3例新的血管病变,对4例病变血管狭窄程度超过75%的患者进行了靶病变再次血管成形术.结论 老年非ST段抬高ACS患者冠状动脉病变常为复杂、多支病变,对其早期行PCI成功率高,近期及远期疗效良好,主要不良心血管事件发生率低,安全可行.     

替罗非班对急性冠状动脉综合征患者肝剂量及血小板的影响

目的：探讨对急性冠状动脉综合征患者在常规治疗基础上联合替罗非班强化抗血小板治疗对肝素抗凝剂量及血小板数量和功能的影响。资料和方法：选择因急性冠状动脉综合征入院的患者共64例，分为双联抗血小板和肝素抗凝的常规治疗组(n=36)和在此基础上联合使用替罗非班组(n=28)，以达到肝素抗凝使激活的部分凝血时间延长2倍为标准，比较两组肝素使用剂量、ADP诱导的血小板聚集率及血小板数量变化情况。结果：替罗非班组肝素用量（500±120U/h）显著低于常规组(760±148U/h, P<0.01)，用药后两组的血小板聚集率均显著低于用药前(P<0.01)，但替罗非班组降低更显著(P<0.01)，替罗非班组用药后血小板降低(P<0.05)。结论：联合应用替罗非班可降低肝素抗凝剂量，显著抑制血小板聚集活性，并呈降低降低血小板数量的趋势。     

The impact of unfractionated heparin or bivalirudin on patients with stable coronary artery disease undergoing percutaneous coronary intervention

Objectives

To compare bleeding and clinical events of patients with stable angina or silent ischemia undergoing percutaneous coronary intervention (PCI) treated with unfractionated heparin (UFH) or bivalirudin.

Background

Few direct comparisons between UFH monotherapy versus bivalirudin exist for patients with stable ischemic heart disease undergoing PCI.

Methods

A prospective, investigator‐initiated, single‐center, single‐blinded, randomized trial of UFH versus bivalirudin was conducted. The primary endpoint was all bleeding (major and minor) from index‐hospitalization to 30 days post discharge. Secondary endpoints included major adverse cerebral and cardiovascular events (MACCE) and net adverse clinical events (NACE).

Results

Two‐hundred‐sixty patients were randomized for treatment with either UFH (n = 123) (47%) or bivalirudin (n = 137) (53%) There were no significant differences in baseline clinical and angiographic characteristics between the two groups. Primary endpoint was similar in both groups (10.9% with bivalirudin vs 7.3% with UFH [P = 0.31]). Major bleeding rates were 5.8% and 2.4%, respectively (P = 0.17). There was a higher MACCE (3.5% vs 0%, P = 0.03) and NACE (8.8% vs 2.4%, P = 0.03) rate with bivalirudin compared to UFH, respectively. Bivalirudin had increased odds of NACE (OR = 3.65, 95% CI: 1.00‐13.3.6). Death and stent thrombosis rates were low and similar in both groups. Radial access was associated with fewer bleeding events compared to femoral access but not statistically significant (P = 0.29).

Conclusions

Among patients with stable angina or silent ischemia, there was no difference between UFH and bivalirudin in bleeding rates up to 30‐days post‐PCI. MACCE and NACE were higher among the bivalirudin group. Radial access was associated with a numerically lower rate of bleeding compared with femoral access.     

Efficacy of hirudin in reducing cardiovascular events in patients with acute coronary syndrome undergoing early percutaneous coronary intervention.

AIMS: Although hirudin is superior to unfractionated heparin for prevention of death, myocardial infarction, or refractory ischaemia in patients with non-ST-elevation acute coronary syndrome, it is not clear whether hirudin is also of benefit in acute coronary syndrome patients undergoing early percutaneous coronary intervention. METHODS AND RESULTS: In the OASIS 2 trial, 10 141 patients with non-ST-elevation acute coronary syndrome were randomized to 72 h of intravenous hirudin or unfractionated heparin. Percutaneous coronary intervention was performed at the discretion of the investigator. One hundred and seventeen patients underwent percutaneous coronary intervention within the first 72 h ("early percutaneous coronary intervention"). In patients undergoing early percutaneous coronary intervention, hirudin compared with unfractionated heparin was associated with a significantly lower incidence of death or myocardial infarction at 96 h (6.4% vs 21.4%, OR 0.30; 95% CI: 0.10-0.88) and 35 days (6.4% vs 22.9%, OR 0.25; 95% CI: 0.07-0.86). In the unfractionated heparin group, death or myocardial infarction was significantly higher at 35 days in patients undergoing early percutaneous coronary intervention compared with those managed conservatively (22.9% vs 7.3%, OR 3.14, P<0.001) but this early percutaneous coronary intervention-related hazard was not observed in hirudin-treated patients (6.4% vs 6.8%, OR 0.94 P=1.0). A time-dependent covariate for percutaneous coronary intervention was not significant in a Cox regression model, suggesting a similar treatment benefit with hirudin before and after percutaneous coronary intervention. After adjustment for percutaneous coronary intervention propensity, the benefits of hirudin remained significant. There were three major bleeds in patients undergoing early percutaneous coronary intervention, all in patients randomized to hirudin. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome undergoing early percutaneous coronary intervention, a direct thrombin inhibitor such as hirudin may be more effective than heparin in reducing the incidence of ischaemic complications.     

替罗非班对急性冠状动脉综合征肝素剂量及血小板的影响

目的探讨替罗非班对急性冠状动脉综合征患者肝素剂量及血小板计数和功能的影响。方法选择因急性冠状动脉综合征入院患者64例,分为常规治疗组36例和替罗非班组28例,常规治疗组使用抗血小板药和肝素抗凝;替罗非班组在上述基础上联合使用替罗非班,以达到肝素抗凝使激活的部分凝血时间延长2倍为标准,比较两组肝素用量、二磷腺苷（ADP）诱导的血小板聚集及血小板数。结果替罗非班组肝素用量（500±120）U／h显著低于常规组（760±148）U／h,差异有统计学意义（t=7.558,P〈0．01）,用药后两组的血小板聚集率均显著低于用药前（P〈0．01）,但替罗非班组降低更显著（P〈0．01）,替罗非班组用药后血小板数降低（P〈0.05）。结论联合应用替罗非班可降低抗凝肝素剂量,显著抑制血小板聚集,并呈降低血小板数的趋势。     

Utility of a weight-based heparin nomogram for patients with acute coronary syndromes

Abstract
Background:  Unfractionated heparin has been pivotal in the management of acute coronary syndromes (ACS), and continues to be used widely despite the emerging role of low molecular weight heparins (LMWH). The apparent superiority of LMWH over unfractionated heparin may, at least partially, reside in its more predictable achievement of therapeutic effect, with high rates of non-therapeutic activated partial thromboplastin time (APTT) results being observed in the intravenous heparin treatment groups.
Aim:  To evaluate the impact of introduction of a weight-based heparin nomogram developed for use in patients with ACS on frequency of 'therapeutic' APTT results.
Methods:  The effectiveness of an existing non-weight-based heparin nomogram in achieving a therapeutic APTT was compared sequentially with that of a weight-based heparin nomogram in 89 and 84 consecutive patients admitted with a diagnosis of ACS.
Results:  Patients in whom heparin dosage adjustment was weight based rapidly achieved therapeutic APTT. The median time to achieve an APTT within the target range was 8.75 h in the weight-based group versus >24 h in the non-weight-based group. Utilization of a weight-based nomogram was associated with markedly increased proportions of readings within the therapeutic APTT range at 6 h and at 24 h (51% vs . 26% and 72% vs . 36%, respectively).
Conclusions:  The current study confirms the marked superiority of the weight-based heparin regimen for treatment of patients with ACS. The nomogram dramatically facilitated the attainment of therapeutic APTT, and may represent the optimal method for titration of heparin dosage to individual heparin requirements in patients with ACS. (Intern Med J 2003; 33: 18−25)     

急性冠脉综合征患者PCI术后应用国产硫酸氢氯吡格雷的疗效

比较急性冠脉综合征（ACS）患者择期PCI术后国产氯吡格雷（泰嘉,Talcom）和进口氯吡格雷（波立维,Plavix）应用的有效性和安全性。方法：158例行择期PCI的ACS患者随机分为：国产氯吡格雷组和进口氯吡格雷组,各79例。随访12个月以上,观察两组术后不良心血管事件及药物不良反应情况。结果：进口氯吡格雷组心源性死亡1例、非致死性心肌梗死1例、靶血管再次血运重建1例、脑卒中1例。国产氯吡格雷组心源性死亡0例、非致死性心肌梗死1例、靶血管再次血运重建2例、脑卒中1例。两组心血管不良事件发生率无显著差异（5.06%比5.06%,P〉0.05）。药物不良反应：进口氯吡格雷组胃肠道反应5例、出血1例、血小板减少1例。国产氯吡格雷组胃肠道反应7例、出血1例、血小板减少2例,两组不良反应发生率无显著差异（8.86%比12.66%,P〉0.05）。结论：与进口氯吡格雷相比,国产氯吡格雷应用于PCI术后患者是安全、有效的。     

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non–ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.