Enoxaparin in Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction: Treatment Benefits in Prespecified Subgroups

Background: Two large-scale phase III clinical trials, the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trial and the Thrombolysis in Myocardial Infarction (TIMI) 11B study, have shown the low-molecular-weight heparin, enoxaparin, to be more effective than unfractionated heparin (UFH) in reducing the risk of death and severe cardiac events in patients with rest unstable angina and/or non-ST-segment elevation myocardial infarction (NSTEMI). However, patients with NSTEMI acute coronary syndromes are a heterogeneous group. Methods: A meta-analysis using pooled data from ESSENCE and TIMI 11B was performed to examine the efficacy of enoxaparin in different patient subgroups. In addition, a statistical model was developed to test which factors best predicted an enhanced treatment effect. Results: Enoxaparin was more effective than intravenous dose-adjusted UFH in reducing the incidence of the composite endpoint (including death, myocardial infarction or recurrent angina prompting urgent revascularization) in the majority of subgroups at 43 days after randomization. Univariate analyses revealed that there was a greater benefit with enoxaparin in patients with ST-segment deviation or elevated cardiac enzyme markers on admission, women, nonsmokers and patients with characteristics indicative of higher cardiac risk, including prior percutaneous coronary interventions, being at least 65 years old, prior angina and prior aspirin use. Multivariate statistical modelling of treatment effect revealed that ST-segment depression and electrocardiographic changes were the best predictors of an enhanced treatment effect. Conclusions: These data reinforce previous evidence suggesting that enoxaparin administered subcutaneously twice daily may be considered as an alternative to intravenous UFH in the acute treatment of a broad range of patients with unstable coronary artery disease. Abbreviated Abstract: Two clinical trials have shown the low-molecular-weight heparin, enoxaparin, to be more effective than unfractionated heparin in reducing risk of death and severe cardiac events in patients with rest unstable angina or non-ST-segment elevation myocardial infarction. A meta-analysis using pooled data was performed to examine the efficacy of enoxaparin in different patient subgroups. A statistical model was developed to aid prediction of enhanced treatment effect. The greater efficacy of enoxaparin in comparison with unfractionated heparin was demonstrated in the majority of patient groups. Statistical modeling of treatment effect showed ST-segment depression and electrocardiographic changes to be the best predictors of an enhanced treatment effect.     

Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE Study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events

OBJECTIVES: We sought to determine whether the observed benefits of enoxaparin were maintained beyond the early phase; a one-year follow-up survey was undertaken for patients enrolled in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) study. BACKGROUND: We have previously reported a significant benefit of low molecular weight as compared with unfractionated heparin (UFH) in the 14- and 30-day incidence of a composite end point of death, myocardial infarction (MI) or recurrent angina in patients with unstable angina or non-Qwave MI. METHODS: The study recruited 3,171 patients with recent-onset rest angina and underlying ischemic heart disease. All patients received oral aspirin daily and were randomized to receive enoxaparin subcutaneously every 12 h or UFH (intravenous bolus followed by continuous infusion) in a double-blind, double-dummy fashion for a median of 2.6 days. RESULTS: The incidence of the composite triple end point at one year was lower among patients receiving enoxaparin as compared with those receiving UFH (32.0% vs. 35.7%, p = 0.022), with a trend toward a lower incidence of the secondary composite end point of death or MI (11.5% vs. 13.5%, p = 0.082). At one year, the need for diagnostic catheterization and coronary revascularization was lower in the enoxaparin group (55.8% vs. 59.4%, p = 0.036 and 35.9% vs. 41.2%, p = 0.002, respectively). CONCLUSIONS: In patients with unstable angina or non-Qwave MI, enoxaparin therapy significantly reduced the rates of recurrent ischemic events and invasive diagnostic and therapeutic procedures in the short term with sustained benefit at one year.     

How should patients with unstable angina and non-ST-segment elevation myocardial infarction be managed? A meta-analysis of randomized trials

PURPOSE: Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may be managed with either an "invasive" or "conservative" strategy. It is unclear which of these strategies is superior. METHODS: We identified studies with MEDLINE and EMBASE searches (1966-September 2003) and by reviewing reference lists. Studies were included if they were randomized controlled trials comparing management strategies for patients in the early post-unstable angina/non-ST-segment elevation MI period and had follow-up data for at least 3 months. RESULTS: Seven trials that randomized a total of 9212 patients were included. The pooled odds ratio (OR) for all-cause mortality was 0.96 (95% confidence interval [CI]: 0.72 to 1.27). The occurrence of fatal or nonfatal re-infarction was reduced with an invasive strategy (OR 0.73; 95% CI: 0.61 to 0.88) as was readmission to hospital (OR 0.67; 95% CI: 0.48 to 0.94). The endpoints of nonfatal MI and the composite of death or nonfatal MI showed nonsignificant trends favoring an invasive strategy. Trials that included a higher proportion of patients with ST-segment depression on admission and trials in which a larger proportion of patients underwent revascularization showed a greater magnitude of benefit for an invasive strategy. CONCLUSION: For patients with unstable angina/non-ST-segment elevation MI, an invasive strategy reduces rates of fatal or nonfatal re-infarction and hospital readmission, but not all-cause mortality, when compared with a noninvasive strategy. These results suggest that an invasive management strategy should be considered for all patients with unstable angina/non-ST-segment elevation MI and perhaps in particular those with ST-segment depression.     

The management of unstable angina and non-ST-segment elevation myocardial infartion

Patients presenting with unstable angina and non-ST elevation myocardial infarction (UA/NSTEM) have a highly variable course. Optimal management is critical because of the high risk of death or myocardial infarction (MI) in the ensuing 30 days. In this article, we review the therapeutic options available to clinicians. Anti-ischemic therapy with beta-blockers and nitrates should be considered in all patients without contraindications. Aspirin remains a cornerstone of antiplatelet therapy and has been shown to substantially reduce the risk of death or MI. Although the data are less robust, unfractionated heparin (UFH) also appears to be efficacious, and the low-molecular-weight heparin (LMWH) enoxaparin appears to be superior to UFH. The GP IIb/IIIa inhibitors, highly beneficial in the setting of percutaneous coronary intervention (PCI), should be considered in patients with continuing ischemia or other high-risk features. The ADP receptor blocker clopidogrel has been shown to be beneficial in patients who are managed conservatively and in those who undergo PCI. Lastly, a strategy of early angiography should be considered in patients with recurrent ischemia or in those who present with high-risk features such as elevated troponins or ST deviation. Thus, early risk stratification using clinical features, electrocardiographic data, and biomarkers allows identification of subgroups of patients who are not only at high risk but also enjoy the greatest benefits from these aggressive therapies and thereby enables clinicians to target these interventions most effectively.     

Prior aspirin users with acute non-ST-elevation coronary syndromes are at increased risk of cardiac events and benefit from enoxaparin

BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.     

A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: The purpose of this study was to compare the effect of receiving pretreatment with antithrombin before randomization as well as overall efficacy and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results demonstrated noninferiority in outcomes with enoxaparin compared with UFH. Randomized treatment was independent of prerandomization treatment. METHODS: Analyses were first performed on the 4 prerandomization subgroups: patients who received no antithrombin therapy and those who were treated with enoxaparin or UFH or both. Then, we focused on the subgroup of patients who received no pretreatment or were pretreated with and randomized to the same drug. Of the 9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received consistent therapy through randomization. The primary end point was the composite of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After adjustment for differences among the subgroups, no significant difference in the association between the 4 pretreatment groups and death or MI remained (p = 0.171). The randomized treatment effect on 30-day death or MI tended to vary with pretreatment (p = 0.055 for interaction test after adjustment). Patients who received consistent therapy with enoxaparin had significantly less death or MI than patients randomized to UFH (adjusted p = 0.041) with a trend toward increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before randomization had potential impact on comparison of study drug effects. After adjustment for differences in baseline characteristics between subgroups, consistent therapy with enoxaparin might be superior to UFH in reducing death or nonfatal MI, with a modest excess in bleeding.     

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 TETAMI Trial: The Safety and Efficacy of Subcutaneous Enoxaparin versus Intravenous Unfractionated Heparin and of Tirofiban versus Placebo in the Treatment of Acute Myocardial Infarction for Patients Not Thrombolyzed: Methods and Design

Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non–Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.     

Use of anticoagulants in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention: a potential role for enoxaparin

Unfractionated heparin (UFH) is currently given as the standard anticoagulant therapy in ST-elevation myocardial infarction (STEMI) patients, including those undergoing percutaneous coronary intervention (PCI). Recent data, however, have shown lower rates of death or recurrent myocardial infarction (MI) with the low-molecular-weight heparin (LMWH) enoxaparin compared with UFH in STEMI patients treated with thrombolytics, off-setting an increase in major bleeding. This review compares the use of enoxaparin with UFH in STEMI patients undergoing PCI, within the context of available evidence for other anticoagulant drugs. Evidence is accumulating for the preferential use of enoxaparin in STEMI patients undergoing PCI.     

Enoxaparin 0.3 mg/kg IV supplement for patients transitioning to PCI after subcutaneous enoxaparin therapy for NSTE ACS: A subgroup analysis from the SYNERGY trial

Objective : To explore clinical and bleeding outcomes in patients enrolled in the SYNERGY trial who had percutaneous coronary intervention (PCI) based on adherence to the dosing regimens of enoxaparin mandated by the protocol. Background : In SYNERGY, 4,687 patients underwent PCI during index hospitalization. Patients in the subcutaneous (sc) enoxaparin group were to be given an 0.3 mg/kg IV bolus immediately before PCI if balloon inflation occurred ≥8 hr after their last sc dose of enoxaparin. Methods : The incidence of the 1° efficacy end point (death/myocardial infarction [MI] post PCI and through 30 days), and the rates of post‐PCI in‐hospital TIMI major and GUSTO severe bleeding were compared between patients randomized to unfractionated heparin (UFH) and those randomized to sc enoxaparin who did or did not receive a supplemental IV bolus of enoxaparin in accord with protocol‐mandates. Results : A total of 4,687 patients had PCI; 2,323 were assigned sc enoxaparin and 1,332 received protocol‐mandated IV enoxaparin bolus, while 215 enoxaparin patients received inappropriate IV therapy (either receiving IV enoxaparin before the 8‐hr protocol time or not receiving the IV enoxaparin as directed after 8 hr). Death or MI occurring post PCI through 30‐day follow‐up tended to be lower in the enoxaparin patients who were treated according to protocol than in those who were not (12.3% vs. 14.4%; adjusted P = 0.25), as was TIMI major bleeding (3.0% vs. 4.7%, adjusted P = 0.08). Conclusion : These exploratory analyses show that patients in SYNERGY who received the protocol‐mandated supplemental IV bolus of 0.3 mg/kg enoxaparin before PCI performed 8–12 hr after their last sc enoxaparin dose tended to have improved outcomes compared with those who did not. Strategies to ensure adherence to dosing guidelines of enoxaparin during PCI should be considered. © 2009 Wiley‐Liss, Inc.     

冠心病介入治疗中应用低分子肝素与普通肝素的随机对照研究

目的探讨冠心病患者经皮冠状动脉介入治疗（PCI）中应用低分子肝素（LMWH）替代普通肝素（UFH）的安全性和有效性。方法自2003年10月至2005年2月共入选966例申请一次性行PCI的患者,所有患者均签署了知情同意书。966例患者中最终完成PCI治疗者455例[包括283例为非ST段抬高急性冠脉综合征（ACS）者]。未接受PCI治疗者511例。研究采用随机对照方法,将入选患者分为LMWH组和静脉UFH组,LMWH组484例,静脉UFH组482例。LMWH组采用依诺肝素（enoxaparin）,按1mg／kg的剂量于PCI手术前至少给予2次皮下注射（每12h一次）,PCI手术在最后1次皮下注射30min后开始。完成冠状动脉造影或PCI后,立即拔出鞘管。静脉UFH组的患者于手术前即刻先给予普通肝素25rIlg静脉推注,如果造影显示适合PCI时,再追加65mg。完成PCI后4h左右拔出鞘管。LMWH组和静脉UFH组中最终行PCI者各为227例和228例。结果（1）LMWH组中1例于PCI术中发生急性血栓形成致急性心肌梗死（AMI）,PCI术后及住院期间未见急性和亚急性血栓形成。静脉UFH组术中和住院期间无急性和亚急性血栓形成。住院期间心脏事件发生率（死亡、AMI和再次血管重建）在LMWH组为0．44％,静脉UFH组为0;（2）LMWH组均于术后即刻拔出鞘管,穿刺局部发生血肿8例,静脉UFH组于术后4h左右拔出鞘管,穿刺局部发生血肿20例,前者血肿发生率明显低于后者,差异有统计学意义（P〈0．05）;（3）随访1个月LMWH组心脏事件发生率为0,静脉UFH组1例于院外发生亚急性血栓致AMI,再次行PCI成功,随访期间心脏事件发生率为0．43％。结论本研究结果提示对于拟行PCI的冠心病患者或非sT段抬高ACS患者术前给予至少2次依诺肝素皮下注射（1mg／kg,每12h一次）,并于最后1次皮下注射的8h内行PCI是安全和有效的,术前和术中不需要给予静脉UFH,术后可即刻拔出鞘管。     

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.     

Is the use of unfractionated heparin in acute coronary syndrome outmoded?

Because of the key role of thrombin in the pathogenesis of acute coronary syndrome (ACS), the appropriate selection of antithrombotic therapy is important. Unfractionated heparin (UFH) has been the agent of choice for decades. Unfortunately, UFH has a number of limitations related to its pharmacokinetic and pharmacodynamic properties. Low molecular weight heparins (LMWHs) are attractive alternatives to UFH for several reasons, including predictable anticoagulation and ease of administration. Two LMWHs (dalteparin and enoxaparin) have been approved as alternatives to UFH in patients presenting with unstable angina and non-ST-segment elevation myocardial infarction. Randomized, controlled trials, in addition to open-label series, indicate that LMWH can safely be the agent of choice with or without glycoprotein IIb/IIIa in the medical and upstream management of patients with ACS. Although the data are not definitive, several trials suggest that given intravenously, enoxaparin is safe as the sole antithrombotic agent in the catheterization laboratory.     

Macroscopic thrombus formation on angioplasty equipment following antithrombin therapy with enoxaparin.

Increasing evidence suggests that treatment with the low molecular weight heparin enoxaparin during percutaneous coronary intervention (PCI) is safe and effective. We evaluated the incidence and consequences of periprocedural macroscopic thrombus formation on PCI equipment following antithrombin therapy with enoxaparin. Between April 2003 and December 2004, all patients undergoing cardiac catheterization following antithrombin therapy with enoxaparin were evaluated. All patients had blood sampled at the onset of procedure for subsequent measurement of anti-factor-Xa levels. Of the 4,504 patients who underwent PCI during this period, in 122 (3%) the procedure was performed within 8 hr of treatment with subcutaneous enoxaparin and no additional unfractionated heparin (UFH) was used periprocedurally. Of these, macroscopic thrombus was observed on PCI equipment in 6 patients (5%) necessitating withdrawal of all catheters and wires. All patients had therapeutic anti-factor-Xa levels at the time of PCI, and had been treated with double antiplatelet therapy with aspirin and clopidogrel. No periprocedural thrombus was observed in 356 patients who were >12 hr of the last dose of enoxaparin and received UFH at the time of PCI. Following observation of thrombus, additional anticoagulation with UFH resulted in significant epistaxis in one patient. In another patient, the procedure was complicated by distal coronary embolization. Percutaneous coronary intervention following antithrombin therapy with enoxaparin is associated with a 5% incidence of macroscopic thrombus formation on PCI equipment. The necessity for subsequent exchange of all equipment and/or the need for additional anticoagulation may have disastrous consequences for the patient. Our findings suggest that the safety of antithrombin therapy with low molecular weight heparin during PCI requires further evaluation.     

The activated clotting time (ACT) can be used to monitor enoxaparin and dalteparin after intravenous administration

BACKGROUND: The use of low-molecular weight heparin (LMWH) during percutaneous coronary intervention (PCI) has been limited by the presumed inability to monitor its anticoagulant effect using bedside assays. OBJECTIVES: This study was designed to compare the dose-response of enoxaparin, dalteparin and unfractionated heparin (UFH) on the activated clotting time (ACT), and to determine whether the ACT or aPTT can be used to monitor intravenous (IV) low molecular weight heparin (LMWH). METHODS: A total of 130 patients undergoing cardiac catheterization were assigned to intravenous enoxaparin 0.5 mg/kg, dalteparin 50 international units/kg or UFH 50 units/kg. Of the 130 patients, 46 (35%) underwent PCI, all of whom received a glycoprotein (GP) IIb/IIIa inhibitor. We measured ACT, activated partial thromboplastin time (aPTT) and plasma anti-Xa levels after serial sampling. RESULTS: Both enoxaparin and dalteparin induced a significant rise in the ACT and aPTT, with an ACT dose-response approximately one-half the magnitude of that obtained using UFH. The time course of changes in the ACT and aPTT after administration of enoxaparin and dalteparin was virtually identical, with a return to baseline at approximately 2 hours. The enoxaparin and dalteparin-treated patients successfully underwent PCI with no major hemorrhagic complications. CONCLUSIONS: The ACT is equally sensitive to IV enoxaparin and dalteparin. These data support an ACT-guided strategy for intravenously administered LMWH during PCI. Additional studies with larger patient populations may be indicated to determine the ideal target ACT for LMWH in PCI.     

A critical review of clinical trials for low-molecular-weight heparin therapy in unstable coronary artery disease.

Unstable angina and non-ST-segment elevation myocardial infarction (MI) are collectively referred to as unstable coronary artery disease (UCAD). They are conditions that share a common pathophysiology and represent frequently encountered, potentially life-threatening clinical manifestations of advanced atherosclerosis. Therefore, treatment of UCAD is a major focus for practicing clinicians, and although pharmacologic agents have been developed that impact on patient outcome, recent data suggest that a further reduction in ischemic complications is possible. Acute-phase treatment with aspirin is associated with a significant reduction in death and nonfatal 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 treatment alternative to UFH in patients with UCAD. The optimal duration of treatment with LMWH is an important question influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. Early trials, such as FRISC and FRIC, demonstrated the benefit of acute therapy with dalteparin sodium; however, the results of extended treatment with dalteparin were inconclusive. The extended phase of these studies included relatively low-risk patients, and a once-daily, relatively low-dose strategy was employed. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin, suggest a benefit for at least 60 days with extended treatment in high-risk patients with UCAD. 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 for up to 45 days, especially those awaiting percutaneous coronary intervention. Extended treatment with dalteparin therefore provides a protective "bridge" to enhance the outcome of patients with UCAD awaiting revascularization.     

New approaches to diagnosis and management of unstable angina and non-ST-segment elevation myocardial infarction

Recently, it has been demonstrated in multiple clinical research studies that non-Q-wave myocardial infarction shares many of the features of unstable angina pectoris and that both diseases initially are managed similarly. Important new antiplatelet drugs (glycoprotein IIb-IIIa inhibitors) and antithrombin agents (low-molecular-weight heparin) are currently recommended for patients with unstable angina pectoris/non-ST-segment elevation MI who are at high or intermediate risk on the basis of symptoms, electrocardiographic findings, and the presence or absence of serum markers (eg, troponin I, troponin T, and creatine kinase-MB). This review provides important information concerning the results of clinical studies of glycoprotein IIb-IIIa inhibitors (tirofiban hydrochloride and eptifibatide) when used with unfractionated heparin in patients with this syndrome or with low-molecular weight heparin (enoxaparin sodium) in similar patients. The Thrombolysis in Myocardial Infarction IIIB, Veterans Affairs Non-Q-Wave Infarction Studies in Hospital, and Fast Revascularization During Instability in Coronary Artery Disease II studies evaluating a conservative, ischemia-guided approach vs an early aggressive approach to such patients are presented, with a practical algorithm for treating such patients.     

The use of antithrombotics for acute coronary syndromes in the emergency department: considerations and impact

Evidence-based guidelines for the management of acute coronary syndromes (ACS) identify a central role for unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). A recent study has suggested that interchanging between UFH and LMWH during the course of treatment may be associated with a worse outcome than continued therapy with either form of heparin. Because this has important implications for physicians in the emergency room, this review examines the current evidence for the efficacy and safety of heparins in ACS. In patients with acute myocardial infarction, several studies have shown that LMWHs represent an effective alternative to UFH as an adjunct to thrombolytic therapy and are not associated with an increased risk of major bleeding. In patients with unstable angina or non-ST-segment elevation myocardial infarction, the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events) and TIMI 11B (Thrombolysis in Myocardial Infarction 11B) trials have shown that the LMWH enoxaparin significantly reduces the risk of cardiovascular events, compared with UFH, whereas other trials have shown that the combination of enoxaparin and a glycoprotein IIb/IIIa antagonist is not associated with an excess risk of bleeding. Recently, newer agents such as fondaparinux and bivalirudin have shown equivalent efficacy to the heparins with less bleeding and appear clinically attractive. Care paths for the use of antithrombotic therapy in patients with ACS are presented based on current US management guidelines and available clinical evidence.     

依诺肝素治疗老年不稳定型心绞痛30例近期疗效观察

目的：观察依诺肝素治疗老年不稳定型心绞痛的近期疗效。方法：将55例老年不稳定心绞痛患者随机分为2组,分别观察依诺肝素组治疗前后心绞痛发作频率,心电图及动态心电图变化和急性心肌梗死,急性血管再通术,院内死亡发生率;并与普通肝素组相对照。结果：依诺肝素组患者心绞痛发作频率明显减少,心电图缺血明显改善;与对照组比较存在明显差异（P＜0．05）,急性心肌梗死,急性血管再通术,院内死亡主要事件总发生率为6．66％,对照组为16％,2组比较差异显著,2组均无严重出血,结论：依诺肝素治疗老年不稳定型心绞痛疗效确切。安全。     

顽固性不稳定性心绞痛的介入治疗

目的　探讨介入治疗顽固性不稳定性心绞痛的近、远期疗效。方法　回顾性分析连续 48例顽固性不稳定性心绞痛患者 ,入院后 (5 .2± 3.4)d介入治疗患者的临床资料。抗血栓治疗为 :阿司匹林、噻氯匹啶、皮下注射低分子量肝素。 48例患者中 ,有 46例 (95 .8% )植入支架。结果　介入治疗的病例、病变成功率分别为 95 .8% (4 6 48)和93.8% (75 80 )。无 1例发生死亡、急性心肌梗死、急诊冠状动脉旁路移植术。 46例介入治疗均获成功 ,心绞痛完全消失或明显缓解。随诊 2～ 2 4(12 .5± 8.0 )个月 ,8例 (17.4% )发生心脏事件 ,其中 2例 (4 .3% )发生心肌梗死 ,6例(13.0 % )再次行血管重建治疗 (介入治疗 5例 ,冠状动脉旁路移植术 1例 )。结论　在使用阿司匹林、噻氯匹啶、皮下注射低分子量肝素抗血栓疗法和广泛应用支架的前提下 ,介入治疗顽固性不稳定性心绞痛成功率高 ,近期疗效明显 ,远期疗效满意