Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction - ENTIRE-TIMI 23


ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab.


ENTIRE-TIMI 23 was designed to evaluate enoxaparin as adjunctive antithrombin therapy with two different pharmacological reperfusion, standard reperfusion using full-dose TNK and combination therapy with half-dose TNK plus abciximab.

Study Design

Study Design:

Patients Enrolled: 483
NYHA Class: not reported
Mean Follow Up: 30 days
Mean Patient Age: not reported
Female: 18
Mean Ejection Fraction: not reported

Patient Populations:

Age 21-75 years Qualifying episode of ischemic discomfort of >=30 minutes duration within the prior 6 hours ST-segment elevation of >=1 mV in 2 limb leads or >=0.2 mV ST-segment elevation in 2 contiguous precordial leads


LBBB, intraventricular conduction defect, or paced rhythm; MI or PCI within the prior 7 days; previous CABG surgery, cardiogenic shock or pulmonary edema; systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg; prior history of stroke, transient ischemic attack, or CNS structural damage; active bleeding or history of hemorrhagic diathesis within prior year; active peptic ulcer disease within 2 months, major surgery within prior 3 months; platelet disorder or thrombocytopenia; need for long-term anticoagulation therapy; treatment with abciximab within the prior 7 days or eptifibatide or tirofiban within the prior 24 hours; known allergy to aspirin or any study drug; treatment with an oral anticoagulant within the prior 5 days, thrombolytic therapy within the prior 7 days, or treatment with any LMWH or UFH within 24 hours prior to randomization; inability to undergo cardiac catheterization; MI precipitated by correctable factors; severe liver disease or estimated creatinine clearance <=30 mL/min.

Primary Endpoints:

TIMI grade 3 flow at 60 minutes in the infarct related artery.

Secondary Endpoints:

TIMI frame count at 60 minutes in the infarct related artery ECG resolution Composite end point of death and recurrent MI at 30 days TIMI major hemorrhage at 30 days

Drug/Procedures Used:

Patients were randomized to either standard reperfusion (full-dose TNK) or combination therapy (half-dose TNK plus abciximab) and to either a control group using UFH or an experimental group using enoxaparin. Full dose TNK bolus was 0.53 mg/kg; combination therapy was half dose TNK bolus of 0.27 mg/kg and abciximab dose of 0.25 mg/kg bolus and 12-hour infusion of 0.125 mg/kg/min. UFH dose was 60 U/kg bolus followed by 12 U/kg/h infusion for >=36 hrs for patients in the standard reperfusion arm; UFH dose was 40 U/kg bolus followed by 7 U/kg/h infusion for >=36 hrs for patients in the combination arm. Both UFH regimens were titrated to aPTT of 1.5-2.5 times control. Enoxaparin dosing was 1.0 mg/kg SC every 12 hours for up to 8 days +/- initial 30 mg IV bolus for patients in the standard reperfusion arm; dosing was 0.3-0.75 mg/kg SC every 12 hours for up to 8 days +/- initial 30 mg IV bolus for patients in the combination arm.

Concomitant Medications:


Principal Findings:

In the full-dose TNK group, the rate of TIMI 3 flow at 60 minutes was 52% with UFH and 48%-51% with enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47%-58% with enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among enoxaparin patients. Death or recurrent MI by 30 days occurred in the full-dose TNK group in 15.9% of UFH patients and 4.4% with enoxaparin (p=0.005), mainly due to a reduction in the rate of nonfatal reinfarction (12.2% with UFH vs 1.9% with enoxaparin, p=0.003). In the combination therapy group, the rates were 6.5% with UFH and 5.5% with enoxaparin. The rate among all UFH patients was 11.3% vs 4.9% in enoxaparin patients (p=0.01). In the full-dose TNK group, the major hemorrhage rate with full-dose TNK was 2.4% with UFH and 1.9% with enoxaparin; with combination therapy, it was 5.2% with UFH and 8.5% with enoxaparin.


Enoxaparin is associated with similar TIMI 3 flow rates as UFH at an early time point. There were clinical benefits over UFH as shown by a reduction in ischemic events through 30 days. The benefits of enoxaparin were achieved with a similar risk of major hemorrhage. The reduction in ischemic events may be due to a combination of greater inhibition of thrombin generation, more stable anticoagulant effect, and a longer treatment with enoxaparin, leading to less thrombus burden and less platelet activation, and possibly lower rates of reocclusion. The positive results of ENTIRE are consistent with results of other trials of enoxaparin in STEMI, including HART II and ASSENT 3.


Circulation. 2002;105:r27-r34.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Myocardial Infarction, Thrombin, Enoxaparin, Thrombosis, Fibrinolytic Agents, Immunoglobulin Fab Fragments, Tissue Plasminogen Activator, Platelet Activation

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