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.     

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.     

ExTRACT-TIMI 25 in perspective: key lessons regarding enoxaparin as an adjunct to fibrinolytic therapy

Unfractionated heparin (UFH) for 48 h has been the traditional standard anticoagulant with fibrinolytics. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction (ExTRACT)-Thrombolysis in Myocardial Infarction (TIMI) 25 trial prospectively studied the usefulness of enoxaparin and found that in patients treated with fibrinolysis, enoxaparin administered throughout the index hospitalization was superior to the standard 48-h UFH infusion. However, enoxaparin increased major bleeding. The data from this large trial were further analyzed across various subgroups and these results support the use of enoxaparin in a broad range of patients. The ExTRACT-TIMI 25 trial employed a novel dosing regimen for enoxaparin adjusted for age and renal function, which was designed to minimize bleeding risk while maintaining the beneficial effects of enoxaparin. Based on the evidence from this trial, the 2007 ST-segment elevation myocardial infarction guidelines now preferentially recommend enoxaparin to be administered throughout the index hospitalization as per the dosing regimen used in ExTRACT-TIMI 25 in most patients treated with fibrinolytic therapy.     

Enoxaparin is superior to unfractionated heparin in patients with ST elevation myocardial infarction undergoing fibrinolysis regardless of the choice of lytic: an ExTRACT-TIMI 25 analysis.

AIMS: We compared outcomes of ST-elevation myocardial infarction (STEMI) patients randomized to a strategy of either enoxaparin or unfractionated heparin (UFH) to support fibrinolysis. METHODS AND RESULTS: In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis in Myocardial Infarction Study 25 (ExTRACT-TIMI 25) trial, 20,479 patients undergoing fibrinolysis for STEMI with a fibrin-specific agent (N = 16,283) or streptokinase (SK) (N = 4139) were randomized to enoxaparin throughout their hospitalization or UFH for at least 48 h. The primary end point of death or nonfatal recurrent MI through 30 days occurred in 12.0% of patients in the UFH and 9.8% in the enoxaparin groups when treated with fibrin-specific lytics [odds ratio(adjusted) (OR(adj)) 0.78; 95% CI 0.70-0.87; P < 0.001] and 11.8 vs. 10.2%, respectively, when treated with SK (OR(adj) 0.83; 95% CI 0.66-1.04; P = 0.10; P(interaction) = 0.58). Major bleeding rates including intracranial hemorrhage within the fibrin-specific cohort were 1.2 and 2.0% in the UFH and enoxaparin groups, respectively (P < 0.001) and 2.0% in UFH and 2.4% in enoxaparin patients in the SK cohort (P = 0.16). Interaction tests between antithrombin- and lytic-type were non-significant (P = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (OR(adj) 0.82; 95% CI 0.74-0.91; P < 0.001) and favoured enoxaparin in the SK cohort (OR(adj) 0.89; 95% CI 0.72-1.10; P = 0.29; P(interaction) = 0.53). CONCLUSION: The benefits of an enoxaparin strategy over UFH were observed in both SK and fibrin-specific-treated STEMI patients. Therefore, an enoxaparin strategy is preferred over UFH to support fibrinolysis for STEMI regardless of lytic agent.     

Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI 25.

AIMS: To determine the effects of age on outcomes in patients with STEMI treated with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX was administered to patients >or=75 years, and a reduced dose in those with an estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a subset of patients (n = 73). The exposure to anti-Xa over time was lower in the elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal recurrent myocardial infarction, was greater in patients < 75 years (20%) than > 75 years (6%), but the absolute benefits were similar. When compared with UFH, ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in both young and elderly patients with STEMI treated with fibrinolysis.     

Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events.

AIMS: To determine whether low-molecular-weight heparin (LMWH)+glycoprotein (GP) IIb/IIIa inhibitors provide greater benefit than unfractionated heparin (UFH)+GP IIb/IIIa inhibitors, irrespective of renal status. METHODS AND RESULTS: Patients in the Global Registry of Acute Coronary Events (GRACE) were divided into three groups according to creatinine clearance (CrCl): normal renal function (CrCl >60 mL/min), moderate renal dysfunction (30相似文献   

A strategy of using enoxaparin as adjunctive antithrombin therapy reduces death and recurrent myocardial infarction in patients who achieve early ST-segment resolution after fibrinolytic therapy: the ExTRACT-TIMI 25 ECG study.

AIMS: To determine the relationship between a strategy of enoxaparin (ENOX), early ST-segment resolution (STRes), and clinical outcomes on patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolysis. METHODS AND RESULTS: Baseline and 180 min ECGs were analysed in 3208 of the 20 479 patients in the ExTRACT-TIMI 25 trial, which randomifzed patients with STEMI to ENOX vs. unfractionated heparin (UFH) as adjunctive therapy. STRes was defined as complete (70%), partial (30-70%), or none (<30%). There was no evidence for a difference in STRes between the groups assigned to the ENOX or UFH (median 69.4 vs. 67.2%; P = 0.13). Among patients with complete STRes (n = 1100), ENOX significantly reduced death or non-fatal recurrent MI at 30 days when compared with UFH (4.4 vs. 9.9%; OR(adj) 0.39; P < 0.001), whereas there was no difference in patients with only partial or no STRes [14.2 vs. 12.5%; OR(adj) 1.0; P = 0.98 (n = 368) and 16.2 vs. 15.9%; OR(adj) 1.0; P = 0.97 (n = 830), P for interaction = 0.008]. CONCLUSION: When compared with UFH, a strategy of ENOX significantly reduces death or non-fatal recurrent MI in patients who achieved complete STRes, but not in patients with less STRes. These data suggest that a strategy of ENOX improves outcomes by preventing re-occlusion in patients achieving initial successful reperfusion after fibrinolytic therapy rather than by facilitating initial reperfusion.     

Safety and effectiveness of enoxaparin following fibrinolytic therapy: Results of the Acute Myocardial Infarction (AMI)-QUEBEC registry

BACKGROUND:

Previous randomized controlled trials and meta-analyses demonstrated the superior efficacy of enoxaparin (ENOX) over unfractionated heparin (UFH) in patients with ST segment elevation myocardial infarction (STEMI). The external validity of randomized controlled trials may be limited by selective inclusion of patients who are younger and healthier than the ‘real-life’ population.

OBJECTIVE:

To evaluate the safety and effectiveness of ENOX compared with UFH in unselected STEMI patients.

METHODS:

The safety and effectiveness of ENOX and UFH were compared in STEMI patients who received fibrinolytic therapy at 17 Quebec hospitals in 2003.

RESULTS:

A total of 498 STEMI patients received systemic anticoagulation, with ENOX and UFH administered in 114 and 384 patients, respectively. There were no differences in baseline characteristics between the two patient groups. The rates of in-hospital major adverse cardiac or cerebral events were 11.4% in the ENOX group compared with 14.0% in the UFH group (P=0.51). In-hospital death or nonfatal reinfarction occurred in 7.9% of patients who received ENOX compared with 9.9% of patients who received UFH (P=0.52). Major bleeding occurred in 4.4% of patients who received ENOX versus 6.0% in patients who received UFH (P=0.51).

INTERPRETATION:

There was no significant difference in the rates of in-hospital adverse events in the ENOX group compared with the UFH group, when used in the real-life context. Larger observational studies may further confirm the safety, effectiveness and optimal duration of the administration of ENOX in unselected STEMI patients treated with fibrinolysis.     

Correlates of bleeding events among moderate- to high-risk patients undergoing percutaneous coronary intervention and treated with eptifibatide: observations from the PROTECT-TIMI-30 trial.

OBJECTIVES: We aimed to identify correlates of Thrombolysis In Mycocardial Infarction (TIMI) major/minor bleeding among eptifibatide-treated patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Evaluation of bleeding predictors among patients treated with glycoprotein IIb/IIIa receptor inhibition might aid in the identification of targets to reduce bleeding risk. METHODS: Data were analyzed from 567 moderate- to high-risk PCI patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) treated with eptifibatide/reduced-dose unfractionated heparin or eptifibatide/reduced-dose enoxaparin enrolled in the Randomized Trial to Evaluate the Relative Protection Against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia Among Anti-Platelet and Anti-Thrombotic Agents-Thrombolysis In Myocardial Infarction-30 (PROTECT-TIMI-30). RESULTS: The incidence of significant bleeding was 3.2% with a median time to event of 7.0 h after the first eptifibatide bolus. Increased age was the only independent correlate of bleeding events. Among patients with reduced creatinine clearance (CrCl), lack of adjustment of the maintenance infusion for CrCl < or =50 ml/min occurred frequently (15 of 33 patients, or 45%) and was associated with a high rate of bleeding (20%). The association of CrCl with bleeding appeared to be largely mediated by the incorporation of age in the estimation of CrCl. Patient gender, Cr, weight, and the peak activated clotting time were not associated with bleeding. CONCLUSIONS: Among NSTEACS PCI patients treated with eptifibatide, increased age was a significant correlate of bleeding events and appeared to explain the association between low CrCl and bleeding. The more widespread use of CrCl or other estimates of renal function over Cr may lead to more appropriate dose adjustments of eptifibatide.     

A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention. Results of the Evaluating Enoxaparin Clotting Times (ELECT) Study

OBJECTIVES: The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND: In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS: We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS: The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every approximately 30-s rise. CONCLUSIONS: Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal.     

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.     

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.     

Low molecular weight heparin and bleeding in patients with chronic renal failure

PURPOSE OF REVIEW: Low molecular weight heparin (LMWH) has largely replaced unfractionated heparin (UFH) in patients with venous thromboembolism because of its pharmacokinetic profile, ease of administration and lack of need for monitoring. The pharmacokinetic profile of LMWH is due to lower molecular weight and reduced charge resulting in less nonspecific protein binding than UFH. These same characteristics make LMWH more dependent on renal function compared with UFH. Consequently, care should be employed when LMWH is administered to patients with impaired renal function as reduced clearance and bioaccumulation may cause bleeding. RECENT FINDINGS: LMWHs vary in their likelihood of bioaccumulation in chronic renal failure. Enoxaparin bioaccumulates and causes bleeding if administered in therapeutic doses without dose adjustment to patients with impaired renal function. Less rigorous evidence suggests that tinzaparin does not bioaccumulate. Bioaccumulation appears to be greatest in patients with a creatinine clearance less than 30 ml/min, and when therapeutic LMWH doses are used. SUMMARY: Care should be used when LMWHs are administered to patients with impaired renal function, particularly those with severe impairment (creatinine clearance below 30 ml/min).     

Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab

OBJECTIVES: The aim of this study was to evaluate percutaneous coronary intervention (PCI) in the Assessment of the Safety and Efficacy of New Thrombolytic Regimens (ASSENT-3) trial. BACKGROUND: In the ASSENT-3 trial, co-therapy with abciximab (ABC) or enoxaparin (ENOX) reduced ischemic complications after ST-elevation acute myocardial infarction treated with tenecteplase when compared with unfractionated heparin (UFH). The effect of these new co-therapies on the results of PCI is unknown. METHODS: Clinical outcomes in patients who received co-therapy with ABC, ENOX, or UFH and subsequently underwent an elective (n = 1,064) or urgent (n = 716) PCI in the ASSENT-3 trial were compared. RESULTS: No significant differences in clinical end points were observed in patients who underwent an elective PCI. A non-significant trend toward fewer in-hospital myocardial re-infarctions was seen with ABC and ENOX when compared with UFH (0.5% vs. 0.6% vs. 1.5%, respectively). The incidence of bleeding complications was similar in the three treatment arms. Significantly fewer ABC- and ENOX-treated patients needed urgent PCI compared with UFH (9.1% vs. 11.9% vs. 14.3%; p < 0.0001), but outcomes in these patients were in general less favorable (30-day mortality: 8.2% vs. 5.4% vs. 4.5%; 1-year mortality: 11.0% vs. 8.5% vs. 5.6%; in-hospital re-infarction: 3.9% vs. 2.5% vs. 2.7%; major bleeding complications: 8.8% vs. 7.0% vs. 3.4%). In pairwise comparisons with UFH, the higher one-year mortality and major bleeding rates after ABC were statistically significant (p = 0.045 and p = 0.012, respectively). CONCLUSIONS: Clinical outcomes after elective PCI were similar with the three antithrombotic co-therapies studied in ASSENT-3. Although fewer patients needed urgent PCI with ABC and ENOX, clinical outcomes were less favorable in this selected population, especially with ABC.     

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.     

Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies

Background

The advantages of enoxaparin over unfractionated heparin (UFH) for the treatment of patients with non-ST-segment elevation acute coronary syndromes are well established. However, no data are available about the safety and efficacy in patients who are obese and patients with severe renal impairment.

Methods

A retrospective analysis of treatment effects was performed on patients who were obese and patients with severe renal impairment from the Efficacy Safety Subcutaenous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials, in which patients were treated with enoxaparin or UFH. The primary composite end point was death, myocardial infarction (MI), and urgent revascularization (UR), and the secondary end points were major and any hemorrhage.

Results

When compared with UFH, enoxaparin reduced the rate of the primary end point in patients who were obese (14.3% vs 18.0%, P = .05), patients who were not obese (16.1% vs 19.2%, P <.01), and patients without severe renal impairment (15.7% vs 18.4%, P <.01). There was no significant difference in major bleeding between enoxaparin and UFH in any of the 4 subgroups. There were no differences in either the primary end point (17.6% vs 16.2%, P = .39) or major hemorrhage (1.3% vs 0.8%, P = .12) in patients who were obese receiving either UFH or enoxaparin compared with patients who were not obese. Patients with severe renal impairment tended toward a higher rate of the primary end point (25.9% vs 17%, P = .09) and experienced more major hemorrhages (6.6% vs 1.1%, P <.0001).

Conclusions

Enoxaparin reduced the rate of the combined end point of death/MI/UR in the subgroups of patients who were obese, patients who were not obese, and patients without renal insufficiency. Obesity did not impact clinical outcomes in the combined analysis of ESSENCE and TIMI 11B. Patients with severe renal impairment have a higher risk of clinical events and major and any hemorrhages than patients without severe renal impairment, whether they are treated with UFH or enoxaparin.     

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.     

Elderly Patients with Acute Coronary Syndromes: Higher Risk and Greater Benefit from Antithrombotic and Interventional Therapies

In elderly patients with acute coronary syndromes, outcomes are poorer than in younger patients and, disappointingly, some therapies—including thrombolysis for ST elevation myocardial infarction—confer less benefit than in younger patients. In contrast, in unstable angina and non-ST elevation myocardial infarction, the elderly appear to derive greater relative and absolute benefit from the newer, more potent antithrombotic therapies. In both the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events and Thrombolysis in Myocardial Infarction 11B trials, the low molecular weight heparin enoxaparin, compared with unfractionated heparin, appeared to have greater relative and absolute benefit in patients aged 65 years and older, as compared with younger patients. For the glycoprotein IIb/IIIa inhibitors, an equivalent relative benefit has been observed, which translated into a greater absolute benefit in older vs. younger patients. Similarly, in the FRagmin and Fast Revascularisation during InStability in Coronary Artery Disease II trial, patients 65 years and older derived significantly greater benefit from an invasive than from a conservative strategy, whereas there was no difference in outcome by strategy in younger patients. A similar trend was observed in the Thrombolysis in Myocardial Infarction IIIB trial. Thus, in unstable angina and non-ST elevation myocardial infarction, elderly patients are at higher risk and appear to derive particular benefit from the more aggressive antithrombotic and interventional therapies.     

Impact of anticoagulation regimens on sheath management and bleeding in patients undergoing elective percutaneous coronary intervention in the STEEPLE trial

Objective: To evaluate the impact of sheath management on bleeding rates. Background: The procedural characteristics and anticoagulant regimen determine the frequency of postoperative bleeding complications following percutaneous coronary intervention (PCI). Methods: This subanalysis of the SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation (STEEPLE) trial evaluated the relative impact of enoxaparin or unfractionated heparin (UFH) on the rate of non‐coronary artery bypass graft‐related major and minor bleeding, according to sheath management procedures in 3,528 patients undergoing elective PCI with a femoral approach. Results: Sheaths were removed at a median time of 54 min with enoxaparin 0.5 mg/kg, compared with 3 hr 14 min with enoxaparin 0.75 mg/kg and 2 hr 24 min with UFH. Early sheath removal (within 30 min from the end of PCI) was associated with reduced bleeding in patients receiving 0.5 or 0.75 mg/kg enoxaparin compared with UFH (enoxaparin 0.5 mg/kg: 4.9% vs. 10.8%; P < 0.001; enoxaparin 0.75 mg/kg: 5.0% vs. 10.8%; P < 0.001). Compared with UFH, major and minor bleeding was halved when enoxaparin (0.5 mg/kg and 0.75 mg/kg) was used in combination with a closure device (4.4% and 5.3% vs. 10.5% with UFH) or smaller (<7 Fr) sheath sizes (4.9% and 6.0% vs. 9.3%). Conclusion: This analysis shows that early sheath removal can be performed safely following elective PCI in patients receiving enoxaparin. Enoxaparin use was associated with less major and minor bleeding compared with UFH, when either a closure device or a smaller sheath size was used. © 2009 Wiley‐Liss, Inc.     

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.