Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel given together in STEMI remains to be defined. METHODS: We compared the rates of major adverse cardiovascular events (MACE) as well as the rates of bleeding in medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate of the composite of death, recurrent myocardial infarction, myocardial ischemia, or stroke, compared with UFH, both in patients (n = 2,173) treated with clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj) 0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not statistically significantly higher in patients treated with clopidogrel (2.7% vs. 1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH, either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI 0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients who are and are not treated with clopidogrel. The totality of trial data suggest that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an attractive pharmacologic reperfusion strategy in STEMI.     

替格瑞洛与氯吡格雷在急性ST段抬高型心肌梗死急诊PCI中的疗效及安全性探讨

目的探讨替格瑞洛与氯吡格雷在急性ST段抬高型心肌梗死(STEMI)急诊经皮冠状动脉介入术(PCI)中的疗效及安全性。方法选择2015-01~2015-08酒泉市医院心内科接诊的STEMI行PCI治疗的100例患者作为研究对象。根据随机数字表法将患者分为两组,每组50例。在进行PCI术前,对照组给予口服硫酸氢氯吡格雷8片治疗,观察组则口服替格瑞洛2片治疗。以冠脉造影中梗死相关血管血流分级(thrombolysis in myocardial infarction,TIMI)3级比例、支架内血栓发生率、靶向血管再狭窄发生率、心血管不良事件发生率、术后出血发生率与药物不良反应发生率为评价指标。结果术前两组TIMI 3级患者比例相当(P0.05),术后两组TIMI 3级比例均大幅上升(P0.05),但观察组上升幅度更为明显(P0.05)。对照组支架内血栓发生率为6.00%,与观察组的4.00%差异无统计学意义(P0.05),观察组靶向血管再狭窄发生率为2.00%,与对照组的6.0%差异无统计学意义(P0.05)。两组心血管不良事件、术后出血及药物不良反应发生率差异均无统计学意义(P0.05)。结论替格瑞洛与氯吡格雷相比急性STEMI急诊PCI中可更加迅速地抑制血小板聚集,降低靶向血管再狭窄发生率,不增加心血管不良事件发生率、术后出血发生率及药物不良反应发生率。     

Low-molecular-weight heparin in patients with acute ST-segment elevation myocardial infarction

One of the primary goals of physicians treating patients presenting to a hospital with acute ST-segment elevation myocardial infarction is to restore the flow of blood in the infarct-related artery as quickly as possible. Prompt and successful reperfusion limits the size of the myocardial infarction, reduces left ventricular dysfunction, and improves the patient's chance of survival. Approximately two thirds of patients with ST-segment elevation myocardial infarction do not present to a hospital capable of conducting urgent direct percutaneous coronary intervention or cardiac surgery when it is needed. They must receive pharmacological reperfusion therapy, a combination of fibrinolytic, antiplatelet, and anticoagulant drugs. Earlier and simpler administration of pharmacological reperfusion therapy could result in significantly improved outcomes. Fibrinolytic therapy, in combination with adjunctive antithrombin therapy that is simpler and quicker to administer (e.g., tenecteplase with enoxaparin), may be more efficacious and easier to use than regimens involving unfractionated heparin.     

Comparison of enoxaparin versus unfractionated heparin in patients with unstable angina pectoris/non-ST-segment elevation acute myocardial infarction having subsequent percutaneous coronary intervention

Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may undergo invasive revascularization procedures shortly after admission to hospital or after a brief period of stabilization. In the Thrombolysis In Myocardial Infarction (TIMI) 11B trial and Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial 1,326 patients underwent percutaneous coronary intervention (PCI). A total of 924 patients underwent PCI during the initial hospitalization period, and of these, 445 patients did so while receiving treatment with unfractionated heparin (UFH) or the low-molecular-weight heparin, enoxaparin. This analysis compared efficacy and clinical events in the enoxaparin and UFH groups in patients who: (1) underwent PCI while on treatment versus those who did not, and (2) underwent PCI in hospital. We also compared those who did not undergo PCI. Treatment with enoxaparin (1 mg/kg given as twice daily subcutaneous injections) was beneficial and well tolerated in patients with unstable angina and non-ST-segment elevation MI who underwent PCI. Compared with UFH, enoxaparin significantly reduced the likelihood of clinical events (death and nonfatal MI after PCI) in patients who underwent PCI after 1 year (p = 0.003 for in-hospital PCI; p = 0.005 for on-treatment PCI), with a trend toward a reduced event rate at 43 days. In addition, patients treated with enoxaparin who did not undergo PCI also showed a reduction in the risk of death, nonfatal MI, and urgent revascularization when compared with those treated with UFH (significant at 43 days, with a trend persisting at 1 year). Study limitations were that PCI was nonrandomized, the analysis was post hoc, and the sample size was relatively small. Nevertheless, in the absence of large clinical trials, this study suggests that treatment with enoxaparin was well tolerated, and exhibited a similar risk of major hemorrhage to UFH in patients who underwent PCI.     

Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-TIMI 25 trial.

OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and subsequently undergo percutaneous coronary intervention (PCI) by analyzing data from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial. BACKGROUND: Limited data are available on the use of ENOX compared with UFH as adjunctive therapy in STEMI patients treated with fibrinolytic therapy and subsequent PCI. METHODS: A total of 20,479 STEMI patients who received fibrinolytic therapy were randomized to a strategy of ENOX throughout index hospitalization or UFH for at least 48 h, with blinded study drug to continue if PCI was performed. The primary end point of death or recurrent MI through 30 days was compared for ENOX versus UFH among the patients who underwent subsequent PCI (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027). Among patients who underwent PCI by 30 days, the primary end point occurred in 10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p = NS). Results were similar when PCI was carried out in patients receiving blinded study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration was associated with a reduced risk of death or recurrent MI without difference in the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy followed by PCI is superior to UFH and provides a seamless transition from the medical management to the interventional management phase of STEMI without the need for introducing a second anticoagulant in the cardiac catheterization laboratory.     

The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial

OBJECTIVES: The aims of the Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI) study were to demonstrate that enoxaparin was superior to unfractionated heparin (UFH) and that tirofiban was better than placebo in patients with acute ST-segment elevation myocardial infarction (STEMI) who do not receive timely reperfusion. BACKGROUND: An optimal treatment strategy has not been identified for the many STEMI patients ineligible for acute reperfusion. METHODS: A total of 1224 patients were enrolled in 91 centers in 14 countries between July 1999 and July 2002. Patients with STEMI ineligible for reperfusion were randomized to enoxaparin, enoxaparin plus tirofiban, UFH, or UFH plus tirofiban. All patients received oral aspirin. The primary efficacy end point was the 30-day combined incidence of death, reinfarction, or recurrent angina; the primary analysis was the comparison of the pooled enoxaparin and UFH groups. REULTS: The incidence of the primary efficacy end point was 15.7% enoxaparin versus 17.3% for UFH (odds ratio 0.89 [95% confidence interval CI = 0.66 to 1.21]) and 16.6% for tirofiban versus 16.4% for placebo (odds ratio 1.02 [95% CI 0.75 to 1.38]). The Thrombolysis In Myocardial Infarction (TIMI) major hemorrhage rate was 1.5% for enoxaparin versus 1.3% for UFH (odds ratio 1.16 [95% CI 0.44 to 3.02]) and 1.8% versus 1% for tirofiban versus placebo (odds ratio 1.82 [95% CI 0.67 to 4.95]). CONCLUSIONS: This study did not show that enoxaparin significantly reduced the 30-day incidence of death, reinfarction, and recurrent angina compared with UFH in non-reperfused STEMI patients. However, enoxaparin appears to have a similar safety and efficacy profile to UFH and may be an alternative treatment. Additional therapy with tirofiban did not appear beneficial.     

Excess heparin dosing among fibrinolytic-treated patients with ST-segment elevation myocardial infarction

Background

Although the use of heparin with fibrinolytics is associated with more rapid ST-segment resolution and increased infarct-related artery patency among patients with ST-segment elevation myocardial infarction (STEMI), its associated increase in bleeding risk is well documented and might be augmented by excess heparin dosing.

Methods

We sought to characterize the incidence and associated bleeding risk of excess heparin dosing among patients with STEMI treated with fibrinolysis who were enrolled in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines initiative. Excess dosing was defined as a bolus more than 60 U/kg or an infusion more than 12 U/kg/h per American College of Cardiology/American Heart Association guidelines and was further stratified into major and mild excess (major defined as a bolus > 70 U/kg or infusion >15 U/kg/h).

Results

Among 964 fibrinolytic-treated patients with STEMI, 758 (79%) received adjunctive unfractionated heparin therapy. Of these, 368 patients (49%) received excess dosing of unfractionated heparin and 137 patients (18%) received major excess heparin dosing. Factors significantly associated with excess dosing included low body weight and female sex. Patients who received major excess dosing had higher unadjusted rates of major bleeding (19.2% vs 12.4%, P = .004) and transfusion (13.5% vs 4.7%, P = .0002) than patients without excess dosing. After adjustment, a trend persisted for the association with higher transfusion risk (odds ratio 1.39 [0.61-3.14]).

Conclusion

Approximately half of fibrinolytic-treated patients with STEMI in contemporary practice received an excess dose of unfractionated heparin. Careful attention to dosing is needed to limit the compounded bleeding risk when heparin is added to fibrinolytic therapy.     

Comparison of effectiveness of enoxaparin versus unfractionated heparin to reduce silent and clinically apparent acute myocardial infarction in patients presenting with non-ST-segment elevation acute coronary syndrome

Electrocardiographic (ECG) estimates of myocardial infarct size based on the Selvester ECG score have been shown to predict mortality and left ventricular function after acute myocardial infarction (AMI). This score has also been used to identify not clinically apparent AMI ("silent" AMI) and to determine treatment effect, suggesting it could serve as a clinical trial end point. The objective of this study was to compare the rate of silent AMI as measured by the Selvester QRS score in patients with a non-ST-segment elevation acute coronary syndrome treated with enoxaparin versus intravenous unfractionated heparin who were participating in a continuous ECG monitoring substudy of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study (ESSENCE) and INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs 6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In conclusion, enoxaparin significantly decreased the composite of silent AMI or clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).     

尿激酶联合氯吡格雷阿司匹林治疗急性ST段抬高型心肌梗塞疗效

目的：观察尿激酶溶栓联合氯吡格雷、阿司匹林治疗急性ST段抬高型心肌梗塞（STEMI）的临床疗效及安全性。方法：87例STEMI符合溶栓治疗患者,被随机分为两组,常规治疗组（40例）和氯吡格雷组（47例）,两组溶栓前均给予阿司匹林0．3g口服,氯吡格雷组于入院后即刻口服氯吡格雷300mg,次日改为75mg,1次／d,口服。观察两组治疗的血管再通率,30d内的主要心血管不良事件（死亡、AMI、恶性心律失常、肺水肿等）的发生率。结果：较之对照组,氯吡格雷组梗塞相关血管再通率明显提高（60．3％：74．5％,P〈0．05）,梗塞后心绞痛发生率、30d死亡及再发心肌梗塞率、严重心律失常发生率、肺水肿发生率均显著下降（P〈0．05）。结论：尿激酶溶栓联合氯吡格雷、阿司匹林治疗急性ST段抬高型心肌梗塞是安全有效的。     

重组人尿激酶原静脉溶栓治疗STEMI的疗效和安全性研究

目的 观察重组人尿激酶原(rhPro-UK) 经静脉溶栓治疗急性ST段抬高型心肌梗死(STEMI)的临床疗效和安全性。 方法 选择汉中市人民医院静脉溶栓治疗的STEMI患者,根据患者溶栓药物不同分为重组人尿激酶原组(n=206)和尿激酶组(n=92),收集两组患者的基线资料和冠状动脉造影资料,比较两组患者临床冠脉再通率、冠脉造影TIMI≥2级开通率、主要出血事件和其他并发症发生率。 结果 与尿激酶组患者比较,重组人尿激酶原组临床再通率[164(79.62 %) vs. 52(63.04 %), P<0.01]和TIMI≥2级开通率[149(82.78 %) vs. 50(65.79 %), P<0.01]显著提高,且主要出血事件[15(7.8 %) vs. 14(15.22 %), P<0.05]和并发症发生率[5(2.3 %) vs. 8(8.70%), P<0.05]显著降低。 结论 重组人尿激酶原静脉溶栓治疗 STEMI 患者血管再通率优于尿激酶,且出血事件及其他并发症发生率低。     

急性ST段抬高型心肌梗死溶栓过程中普通肝素及依诺肝素的应用比较

目的 比较普通肝素及依诺肝素在瑞替普酶治疗急性ST段抬高型心肌梗死（STEMI）中的差异。 方法 将70例STEMI患者按给药方式分为普通肝素组和依诺肝素组，每组35例。两组均采用瑞替普酶进行溶栓治疗，普通肝素组溶栓前先静脉注射普通肝素4 000 U负荷量，接着以12 U/（kg?h）维持静脉滴注48 h，根据活化部分凝血酶时间（APTT）调整普通肝素剂量，48 h后逐渐减量改用皮下注射依诺肝素40 mg，2次/d，序贯治疗(2～7) d或至转运。依诺肝素组溶栓前先给予依诺肝素30 mg静脉注射，15 min后1 mg/kg皮下注射，1次/12 h，治疗(2～7 )d或至转运。比较两组患者临床治疗效果，统计并发症发生率，并进行成本-效果分析。 结果 60 min时普通肝素组再通率为83%，依诺肝素组为57%，120 min时普通肝素组再通率为100%，依诺肝素组为91%，普通肝素组明显高于依诺肝素组（P<0.05）；普通肝素组临床再通时间显著短于依诺肝素组（P<0.05）；普通肝素组肌钙蛋白I（TnI）、肌酸激酶同工酶（CK-MB）峰值显著低于依诺肝素组（P<0.05）；普通肝素组并发症总发生率显著低于依诺肝素组（P<0.05）；普通肝素组成本-效果比显著低于依诺肝素组（P<0.05）。 结论 用瑞替普酶进行溶栓治疗STEMI时，先用普通肝素冲击并足量维持48 h后用依诺肝素序贯治疗较全程应用依诺肝素方便、经济、安全、疗效显著。     

急性ST段抬高型心肌梗死患者直接PCI术后口服替格瑞洛与氯吡格雷疗效比较

目的评估替格瑞洛对接受直接经皮冠状动脉介入术(PCI)的急性ST段抬高型心肌梗死(STEMI)患者抗血小板治疗的临床疗效及安全性。方法入选诊断STEMI并行直接PCI的164例患者,随机分为替格瑞洛组(40例)和氯吡格雷组(124例)。根据治疗后第5天血小板聚集率结果进而将氯吡格雷组分为非氯吡格雷抵抗(CPGR)组(81例)和CPGR组(43例),CPGR组患者改服替格瑞洛。随访3个月,分析替格瑞洛组和非CPGR组用药后5天、1个月、3个月血小板聚集率、主要不良心血管事件(MACE)(心源性死亡、非致死性心肌梗死、卒中、靶血管再次血运重建、支架内血栓形成、再发心绞痛、心功能不全)和药物不良反应(出血、呼吸困难)发生情况;分析CPGR组换药前后血小板聚集率变化。结果替格瑞洛组治疗后第5天、1个月、3个月的血小板聚集率均明显低于非CPGR组(33.94%±14.90%比53.13%±14.07%,25.26%±8.89%比35.51%±9.45%,24.91%±7.55%比31.57%±9.53%),差异有统计学意义(P0.05);CPGR组换用替格瑞洛1个月后血小板聚集率明显降低(28.33%±8.11%比64.50%±11.38%),差异有统计学意义(t=18.944,P0.05)。随访3个月,替格瑞洛组MACE、轻中度呼吸困难发生率较非CPGR组明显降低,且差异有统计学意义(P0.05)。两组患者在轻微出血方面差异无统计学意义(P0.05)。两组患者均无严重出血及重度呼吸困难者。结论替格瑞洛抗血小板作用明显优于氯吡格雷,且对于CPGR患者安全有效,不良反应较轻微,安全性好。     

Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non-ST-segment elevation acute myocardial infarction.

Patients with unstable angina pectoris (UAP) or non-ST-segment elevation acute myocardial infarction (AMI) are at risk of death or recurrent ischemic events, despite receiving aspirin and unfractionated heparin (UFH). This study investigates the effect of the low molecular weight heparin, enoxaparin, on the incidence of hemorrhage and thrombocytopenia in relation to baseline characteristics and subsequent invasive procedures. Rates of hemorrhage and thrombocytopenia were analyzed for UAP or non-ST-segment elevation AMI in patients included in the prospective, randomized, double-blind Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) study. Patients received either enoxaparin or UFH, plus aspirin, for 2 to 8 days. The overall rate of major hemorrhage (at 30 days) was comparable between the 2 groups (6.5% for enoxaparin vs. 7.0% for UFH, p = 0.6). The rate of major hemorrhage while on treatment was slightly higher in the enoxaparin group, but this was not significant (1.1% vs 0.7% for UFH, p = 0.204), as was the rate of major hemorrhage within 48 hours of coronary artery bypass grafting performed within 12 hours of treatment. However, the rate of minor hemorrhage was significantly higher in the enoxaparin group, with the majority being injection-site ecchymoses or hematomas (11.9% vs. 7.2% with UFH, p <0.001). Thrombocytopenia (platelet count <100,000 per mm(3)) occurred mainly in association with coronary bypass surgery, with a similar rate in both groups. Thus, enoxaparin is a well-tolerated alternative to UFH in the management of UAP or non-ST-segment elevation AMI. Despite the more effective antithrombotic effect, which results in fewer ischemic events, enoxaparin is not associated with an increase in the rate of major hemorrhagic complications, and is not significantly associated with thrombocytopenia, but is associated with an increase in minor injection site ecchymosis.