低分子肝素与普通肝素或阿斯匹林治疗不稳定型心绞痛疗效比较

目的：比较低分子肝素（LMWH）、普通肝素（H）与阿斯匹林单独及联合治疗不稳定型心绞痛（UAP）病人的疗效。方法：UAP患者156例，随机分为1）阿斯匹林（ASP）组，2）阿斯匹林加普通肝素（ASP＋H）组，3）阿斯匹林加低分子肝素（ASP＋LMWH）组。疗程7天并随访观察3－6个月。结果：ASP＋LMWH组心绞痛缓解率显著高于ASP组（91．8％vs58．2％，P＜0．001），与ASP＋H组（80．8％）比较无显著差异性（P＞0．05）。随访观察期间，ASP＋LMWH组心绞痛复发率显著低于ASP组和ASP＋H组（12．0％vs40．6％、40．5％）。ASP组共有7例发生急性心肌梗死，6例猝死，ASP＋H组共有2例发生出血倾向。三组药物治疗前后部分凝血酶原时间，凝血时间无明显变化（P＞0．05）。结论：阿斯匹林加低分子肝素较单用阿斯匹林或加用普通肝素治疗不稳定型心绞痛疗效更好，更安全。     

The use of adjunctive anticoagulants in patients with acute coronary syndrome transitioning to percutaneous coronary intervention

Patients presenting to the Emergency Department (ED) need to be quickly diagnosed, risk-stratified, and treated accordingly. Anticoagulants used in the ED should be easy to use and suitable for all patients with acute coronary syndromes, regardless of treatment strategy. In patients with ST-segment myocardial infarction, current guidelines recommend unfractionated heparin regardless of reperfusion strategy or low-molecular-weight heparin (LMWH) as an alternative in patients undergoing percutaneous coronary intervention (PCI). The LMWH enoxaparin is approved for ST-segment elevation myocardial infarction patients managed medically or undergoing PCI. The recently updated American College of Cardiology/American Heart Association guidelines for patients with unstable angina or non-ST-segment elevation myocardial infarction recommend unfractionated heparin or the LMWH enoxaparin (class IA recommendation), or the factor Xa inhibitor fondaparinux or the direct thrombin inhibitor bivalirudin (class IB recommendation) for patients managed invasively. This review discusses each of these anticoagulant options in the context of patients transitioning to PCI.     

Functional features of acute non-Q-wave myocardial infarction and the influence of pre-hospital treatment with propranalol, heparin and aspirin on the prognosis of the disease

193 patients with their first non-Q-wave myocardial infarction (NQMI) were examined with the aim of studying the functional features of NQMI and estimate the influence of pre-hospital treatment with propranalol (PP), heparin and aspirin. The study found that patients having NQMI with initial ST segment depression, unlike those with initial ST segment elevation, were characterized by diffuse coronary atherosclerosis, evident diastolic dysfunction and left ventricle (LV) remodeling, progressing with the course of time. Early administration of aspirin, heparin and PP reduced LV remodeling, improved diastolic function and prognosis in patients having NQMI with initial ST segment depression.     

Role of low-molecular-weight heparin in invasive management of non-ST-elevation acute coronary syndromes

OBJECTIVE: To review the available literature addressing the role of low-molecular-weight heparin (LMWH) as an alternative to unfractionated heparin (UFH) in percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndromes (NSTEACS). DATA SOURCES: A MEDLINE search (1966-March 2004) identified pertinent articles using the key words acute coronary syndromes, unstable angina, non-ST-elevation myocardial infarction, low-molecular-weight heparin, enoxaparin, dalteparin, glycoprotein IIb/IIIa receptor antagonists, abciximab, tirofiban, eptifibatide, percutaneous transluminal coronary angioplasty, and percutaneous coronary intervention. The references of these articles were reviewed for additional pertinent references. STUDY SELECTION AND DATA EXTRACTION: All human trials of LMWH in PCI for treatment of NSTEACS were evaluated. All pertinent studies were included in the review. DATA SYNTHESIS: Administration of LMWH with or without a glycoprotein IIb/IIIa inhibitor during PCI appears to be similar to UFH in terms of efficacy. LMWH, especially in combination with a glycoprotein IIb/IIIa inhibitor, may increase risk of bleeding compared with UFH. CONCLUSIONS: Available clinical trials do not provide definitive evidence to suggest superiority of LMWH over UFH when managing NSTEACS during PCI; however, dosing strategies are available if an LMWH is to be used in this setting.     

Acute and prolonged treatment with low-molecular-weight heparin therapy in patients with unstable coronary artery disease

Unstable angina and non-ST-segment elevation myocardial infarction (MI) are known as unstable coronary artery disease (UCAD). They are syndromes that share a common pathobiology and represent a frequently encountered and potentially life-threatening medical condition. Acute-phase treatment with aspirin is associated with a significant reduction in death and non-fatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. In contrast, low-molecular-weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response making them an attractive alternative treatment to UFH in patients with UCAD. In several studies, acute-phase treatment with LMWH has been shown to be at least as effective and safe as UFH. The optimal duration of treatment with LMWH is an important question that has been influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. In early trials, such as FRISC (Fragmin during instability in coronary artery disease) and FRIC (Fragmin in unstable coronary artery disease), the results of extended treatment were inconclusive; however, the trial populations included patients of relatively low risk and used a once-daily dosing regimen. In the TIMI 11B (Thrombolysis in myocardial infarction) extended treatment beyond the few days of acute treatment with enoxaparin did not add to the beneficial LMWH effect, but in this study 40% of the high-risk patients did not continue on extended treatment. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin sodium, suggest a benefit for up to 45 days with extended treatment in high-risk UCAD patients. Although an early invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin sodium awaiting percutaneous coronary intervention.     

Evolving role of low-molecular-weight heparins in ST-elevation myocardial infarction

OBJECTIVE: To review the available literature on the efficacy and safety of low-molecular-weight heparin (LMWH) in the treatment of ST-elevation myocardial infarction (STEMI) in patients treated with fibrinolytic therapy or conservative medical management. DATA SOURCES: A MEDLINE search (1966-March 2004) using the key words myocardial infarction, STEMI, LMWH, enoxaparin, and dalteparin identified pertinent articles. The references of these articles were reviewed for additional pertinent references. STUDY SELECTION AND DATA EXTRACTION: All human trials of LMWH in STEMI were evaluated. All pertinent studies were included in the review. DATA SYNTHESIS: LMWH did not show a benefit in STEMI without fibrinolytic therapy. Enoxaparin is similar to intravenous unfractionated heparin (UFH) in combination with nonspecific fibrinolytic therapy with regard to invasive reperfusion markers and 30-day clinical outcomes. Enoxaparin decreases composite endpoints in combination with fibrin-specific fibrinolytic therapy compared with UFH, primarily through a reduction in the incidence of reinfarction at 30 days. Bleeding rates with LMWH in combination with fibrinolytic agents are not greater than those with UFH. CONCLUSIONS: Enoxaparin is a reasonable alternative to UFH in patients with STEMI treated with fibrin-specific fibrinolytic therapy. LMWH in patients managed with nonspecific fibrinolytic therapy or conservative medical treatment does not provide an advantage over standard management. Large clinical trials are ongoing which will provide more definitive recommendations.     

肝素治疗急性冠状动脉供血不足的安全性及停药后再发胸痛现象

目的研究肝素治疗急性冠状动脉供血不足（ACI）时并发症的发生率及其影响因素，总结肝素停药后再发胸痛现象和防止方法，籍以评价肝素治疗的安全性。方法除常规治疗外，给予肝素钠连续静滴．部分患者给予尿激酶静脉溶栓后，继以肝素钠连续静滴。按照联合用药24h内应用肝素钠剂量，肝素治疗期间监测凝血时间以及开药方式不同进行分组。分别观察中、重度出血，轻度出血，过敏反应，血小板减少及开用肝素后心电图恶化，再发胸痛的发生频率，采用X2检验。结果阿斯匹林 肝素治疗ACI的出血并发症发生率与阿斯匹林 肝素 尿激酶组比较，无显著性差异（P＞0.50）；凝血时间（CT）＞18min组比＜11min组轻度出血并发症显著增加（P＜0.005）。肝素用量在18750～25000U/24h组比6250～12500U/24h出血并发症显著增加（P＜0.005)；突然停药后再发胸痛及心电图恶化率为显著高于减量停药及加服阿斯匹林组（P＜0．001）。结论肝素用于治疗ACI不仅有效，而且并发症较少；长期小剂量连续静脉应用肝素是安全的；在停用肝素时，认为逐渐减量后停药，或同时加量服用阿斯匹林，可明显减少肝素停药后再发胸痛现象。     

Enoxaparin in acute coronary syndromes

Enoxaparin is a low-molecular-weight heparin (LMWH) derivative that exerts its anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Unlike its unfractionated heparin (UFH) counterparts, enoxaparin has a greater bioavailability, lower incidence of heparin-induced thrombocytopenia and more stable and predictable anticoagulation, allowing fixed dosing without the need for monitoring. These advantages make it an attractive anticoagulant to be used in acute coronary syndrome management. Indeed, several clinical trials and meta-analyses have consistently demonstrated the efficacy of enoxaparin in reducing cardiovascular events and mortality in this population. Although initial clinical trials with enoxaparin during the early conservative approach suggested superior efficacy without differences in safety compared with UFH, emerging data in the current era of early revascularization approach indicate that superior effects of enoxaparin over heparin in reducing clinical events should be balanced against an increase in major hemorrhagic complications. Enoxaparin is a rational alternative to UFH in patients presenting with either unstable angina/non-ST-elevation myocardial infarction or ST-elevation myocardial infarction, with a clinically modest increase in bleeding complications.     

瑞替普酶并低分子肝素用于急性心肌梗死再灌注治疗的有效性与安全性研究

目的探讨急性心肌梗死(AMI)瑞替普酶静脉溶栓并应用低分子肝素(LMWH)替代普通肝素(UFH)抗凝治疗的安全性与有效性。方法106例AMI患者经瑞替普酶静脉溶栓后,随机分为LMWH组(低分子肝素5000U皮下注射,2次/d)和静脉UFH组(普通肝素静脉泵入24h后改为低分子肝素5000U皮下注射,2次/d),1周后行冠状动脉造影及冠脉介入治疗(PCI)。观察临床再通率、血管开通率、急性期并发症、出血及不良反应的发生率。结果①LMWH组与静脉UFH组相比,临床再通率(82.1%vs78.0%)、血管开通率(78.9%vs75.0%)高,临床再通病例梗死后心绞痛发生率(8.70%vs12.8%)低,但两组之间差异无统计学意义;②LMWH组出血并发症明显低于静脉UFH组(7.14%vs18.0%),差异有统计学意义(P<0.05)。③两组PCI后均予LMWH抗凝治疗,30d内无急性或亚急性支架内血栓形成发生。结论本研究结果提示,瑞替普酶并LMWH用于AMI再灌注治疗是安全、有效、方便的,LMWH用于PCI后抗凝治疗疗效确切。     

The role of tirofiban in acute coronary syndromes

Platelet activation and aggregation play an important and essential role in the formation of intracoronary thrombus in acute coronary syndromes (ACS). ACS still carries unacceptably high rates of morbidity and mortality despite intensive antianginal therapy and the wide use of aspirin and heparin. Two glycoprotein IIb/IIIa receptor inhibitors are now licensed for concomitant use with heparin and aspirin in ACS. Glycoprotein IIb/IIIa receptor inhibitors block the final step for platelet aggregation and fibrinogen binding, thus preventing thrombus formation. Tirofiban is a potent, synthetic, non-peptide and specific glycoprotein IIb/IIIa receptor inhibitor. In three major international trials involving over 7200 patients (PRISM, PRISM-PLUS and RESTORE), tirofiban was shown to be well tolerated and to reduce the risk of ischaemic complications in patients with unstable angina, non-Q-wave myocardial infarction and high-risk patients undergoing revascularisation when used in combination with aspirin and heparin. These and ongoing studies are discussed.     

急性冠状动脉综合征治疗研究进展

不稳定性心绞痛和非Q波心肌梗死是临床上常见急症 ,称之为急性冠状动脉综合征 ,该综合征具有较高发生率和死亡率 ,早期正确处理非常必要。本文作者复习近年来有关文献 ,就急性冠状动脉综合征治疗研究进展作一介绍。     

The role of low-molecular-weight heparins in cardiovascular medicine

Low-molecular-weight heparins (LMWHs) have been shown to be as effective and safe as unfractionated heparin (UFH) for acute phase treatment of acute coronary syndrome in the absence of ST-elevation [unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI)]. LMWHs have practical advantages over UFH, including usual lack of requirement for laboratory monitoring of the anticoagulant response because of their favourable pharmacokinetic properties, and thus represent a simpler and more cost-effective option in clinical practice. The LMWH dalteparin has been shown to provide extended therapy benefit to high-risk UA/NSTEMI patients and can provide a protective bridge until revascularization. While revascularization procedures are now an established intervention for patients with UA/NSTEMI, a new approach for patients who cannot undergo immediate catheter intervention is to continue with medical treatment until revascularization is possible. LMWHs are currently being investigated for use in the catheterization laboratory, in patients undergoing percutaneous coronary intervention procedures, and in conjunction with thrombolytics for treatment of acute myocardial infarction.     

Prognostic value of viable myocardium in patients with non-Q-wave and Q-wave myocardial infarction

This study assessed the amount and prognostic value of myocardial viability in patients with non-Q-wave myocardial infarction (NQMI) and Q-wave myocardial infarction (QMI). A total of 175 patients with MI and an ejection fraction < or = 45% underwent dobutamine stress echocardiography. On the basis of clinical criteria and myocardial viability, 110 patients were revascularized. The amount of viable myocardium and the clinical outcome were compared in the NQMI and QMI groups. Patients with NQMI exhibited a larger amount of viable myocardium compared with those with QMI. The mortality rate was 6% in patients with NQMI with viable myocardium and subsequent revascularization, 33% in patients with NQMI without viable myocardium or revascularization, 27% in patients with QMI with viable myocardium and subsequent revascularization, and 33% in patients with QMI without viable myocardium or revascularization. In conclusion, our data suggest that patients with NQMI and viable myocardium have the best prognosis after revascularization.     

The medical management of acute coronary syndromes and potential roles for new antithrombotic agents

Antithrombic therapy is recommended to prevent ischemic complications in patients with high-risk non-ST-segment elevation acute coronary syndromes, including patients with unstable angina/non-ST-segment elevation myocardial infarction and patients with ST-segment elevation myocardial infarction undergoing fibrinolysis with fibrin-specific agents. Ischemic benefit from these agents must be balanced against an increased risk of bleeding, which may itself carry adverse long-term consequences. Recent trials suggest that the low-molecular-weight heparin enoxaparin may be superior to unfractionated heparin for preventing ischemic complications, although it also may be associated with an increase in bleeding risk. In two other contemporary trials, the Factor Xa inhibitor fondaparinux improved mortality and morbidity in patients with unstable angina/non-ST-segment elevation myocardial infarction and in patients with ST-segment elevation myocardial infarction undergoing fibrinolytic reperfusion, without increasing bleeding risk. These data underscore the promise of new antithrombotic agents to improve outcomes in acute coronary syndrome (ACS) patients being medically managed.     

Anti-platelet drugs (aspirin, ticlopidine, etc)

Previous clinical trials have shown that anti-platelet drugs, such as aspirin and ticlopidine, are approved for prevention of serious cardiovascular events in special populations who are at increased risk of cardiovascular events. Of these trials, the Antithrombotic Trialists' Collaboration (ATT) meta-analysis includes approximately 200,000 patients: Anti-platelet therapy was associated with a 34% reduction in the risk of nonfatal myocardial infarction, a 25% reduction in the risk of stroke, and a 15% reduction in the risk of vascular death. Also in patients with acute coronary syndrome (acute myocardial infarction and unstable angina), both aspirin and ticlopidine have been shown to prevent serious cardiovascular events.     

急性心肌梗死延迟冠状动脉介入治疗的临床研究

目的探讨急性心肌梗死（AMI）延迟冠状动脉介入治疗（PCI）的临床效果。方法将106例AMI患者按随机数字表法分为2组,药物治疗组50例,采用常规药物（肠溶阿司匹林、氯比格雷、他汀类调脂、低分子肝素,据情况予硝酸酯类、血管紧张素转换酶抑制剂、β受体阻滞剂等）治疗;PCI组56例,经药物治疗7～15d后PCI。1年后对2组患者病死率和再发心梗、心绞痛的发生率以及左室射血分数（LVEF）水平的变化进行比较。结果 PCI组再发心梗、心绞痛的发生率明显低于药物治疗组,LVEF明显高于药物治疗组（P〈0.05或P〈0.01）。结论 AMI延迟PCI能改善患者的预后。     

Acute Coronary Syndromes: Diagnosis and Management, Part I

The term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acute myocardial ischemia and includes unstable angina (UA), non—ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). These high-risk manifestations of coronary atherosclerosis are important causes of the use of emergency medical care and hospitalization in the United States. A quick but thorough assessment of the patient''s history and findings on physical examination, electrocardiography, radiologic studies, and cardiac biomarker tests permit accurate diagnosis and aid in early risk stratification, which is essential for guiding treatment. High-risk patients with UA/NSTEMI are often treated with an early invasive strategy involving cardiac catheterization and prompt revascularization of viable myocardium at risk. Clinical outcomes can be optimized by revascularization coupled with aggressive medical therapy that includes anti-ischemic, antiplatelet, anticoagulant, and lipid-lowering drugs. Evidence-based guidelines provide recommendations for the management of ACS; however, therapeutic approaches to the management of ACS continue to evolve at a rapid pace driven by a multitude of large-scale randomized controlled trials. Thus, clinicians are frequently faced with the problem of determining which drug or therapeutic strategy will achieve the best results. This article summarizes the evidence and provides the clinician with the latest information about the pathophysiology, clinical presentation, and risk stratification of ACS and the management of UA/NSTEMI.ACC = American College of Cardiology; ACE = angiotensin-converting enzyme; ACS = acute coronary syndrome; ADP = adenosine diphosphate; AHA = American Heart Association; BNP = B-type natriuretic peptide; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CHF = congestive heart failure; CI = confidence interval; CK-MB = muscle and brain fraction of creatine kinase; CRP = C-reactive protein; CURE = Clopidogrel in Unstable Angina to Prevent Recurrent Events; ECG = electrocardiography; ED = emergency department; GP = glycoprotein; HR = hazard ratio; IV = intravenous; LDL = low-density lipoprotein; LMWH = low—molecular-weight heparin; LV = left ventricular; MI = myocardial infarction; NSTEMI = non—ST-segment elevation MI; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation MI; TIMI = Thrombolysis in Myocardial Infarction; UA = unstable angina; UFH = unfractionated heparinThe term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acute myocardial ischemia and covers the spectrum of clinical conditions ranging from unstable angina (UA) to non—ST-segment elevation myocardial infarction (NSTEMI) to ST-segment elevation myocardial infarction (STEMI). Unstable angina and NSTEMI are closely related conditions: their pathophysiologic origins and clinical presentations are similar, but they differ in severity. A diagnosis of NSTEMI can be made when the ischemia is sufficiently severe to cause myocardial damage that results in the release of a biomarker of myocardial necrosis into the circulation (cardiac-specific troponins T or I, or muscle and brain fraction of creatine kinase [CK-MB]). In contrast, the patient is considered to have experienced UA if no such biomarker can be detected in the bloodstream hours after the initial onset of ischemic chest pain. Unstable angina exhibits 1 or more of 3 principal presentations: (1) rest angina (usually lasting >20 minutes), (2) new-onset (<2 months previously) severe angina, and (3) a crescendo pattern of occurrence (increasing in intensity, duration, frequency, or any combination of these factors). Each year in the United States, approximately 1.36 million hospitalizations are required for ACS (listed either as a primary or a secondary discharge diagnosis), of which 0.81 million are for myocardial infarction (MI) and the remainder are for UA. Roughly two-thirds of patients with MI have NSTEMI; the rest have STEMI.¹     

磺达肝癸钠和低分子肝素治疗急性冠脉综合征疗效比较

对比磺达肝癸钠与低分子肝素(LMWH)在治疗急性冠脉综合征(ACS)中的疗效及安全性.方法 选择2009年11月至2010年8月本院确诊的ACS患者105例,按随机原则分为两组,均给予硝酸酯类、β受体阻滞剂、血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体阻滞剂(ARB)、他汀类、氯吡格雷、肠溶阿司匹林等基础药物治疗;在基础治疗上磺达肝癸钠组(50例)每日1次皮下注射磺达肝癸钠2.5 mg,LMWH组(55例)每日2次皮下注射LMWH 0.4 ml,均连用3～8 d.观察两组治疗期间的临床疗效,以及7 d、30 d时心血管事件和治疗期间出血的发生率.结果 磺达肝癸钠组与LMWH组总有效率比较差异无统计学意义(96.0%比92.7%,P＞0.05);7 d、30 d时心血管事件(死亡、急性心肌梗死和再发心肌梗死)的发生率比较差异也无统计学意义(7 d:4.0%比7.3%,30 d:8.0%比10.9%,均P＞0.05);两组均未发生大出血,磺达肝癸钠组轻微出血发生率明显低于LMWH组(2.0%比32.7%,P＜0.01).结论 应用磺达肝癸钠治疗ACS具有不劣于LMWH的疗效,而且有着良好的安全性,不良反应少,值得推广.     

The use of antiplatelet agents in acute cardiac care.

Antiplatelet therapy with aspirin has long been established as standard therapy in the management of conditions such as ST-elevation myocardial infarction and the acute coronary syndromes (unstable angina and non-ST-elevation myocardial infarction). Recently, several more potent platelet inhibitors have been developed and tested in randomized clinical trials. This article reviews the current state of the art of antiplatelet therapy.     

GLYCOPROTEIN IIB/IIIA ANTAGONISTS: DO THEY HAVE A ROLE IN THE MANAGEMENT OF UNSTABLE ANGINA?

Plaque rupture, platelet aggregation and thrombosis have central roles in the pathogenesis of acute coronary syndromes. Despite several trials showing the benefit of aspirin and heparin in patients presenting with unstable angina and acute myocardial infarction, these patients are still at risk. This has prompted the development and evaluation of several new therapeutic agents including low molecular weight heparin, new antiplatelet drugs (e.g. ticlopidine and clopidogrel), direct thrombin inhibitors, and intravenous and oral glycoprotein IIb/IIIa antagonists. The IIb/IIIa receptor is the final common pathway involved in platelet aggregation. Thus, whatever the stimulus for platelet activation, subsequent aggregation is mediated by the IIb/IIIa receptor binding fibrinogen. A variety of antibody, peptide and non-peptide compounds that block the IIb/IIIa receptor have been developed, and several studies have investigated the role of these agents in patients with acute coronary syndromes both within and outside the setting of percutaneous intervention. This article summarises the studies to date using IIb/IIIa antagonists, and discusses their role in patients with non-ST segment elevation acute coronary syndromes.