ENTIRE-TIMI 23

ENoxaparin and TNK-tPA with or without GP IIb/IIIa Inhibitor as REperfusion strategy – Thrombolysis in Myocardial Infarction 23 (2002)

Condition

Prophylaxis for reocclusion after acute myocardial infarction with ST-elevation (STEMI)

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Objective

To evaluate enoxaparin as adjunctive antithrombin therapy with various forms of pharmacological reperfusion in patients with STEMI

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Trial design

Randomized, open-label, phase II study
Patients were randomized either to full-dose tenecteoplase (TNK, 0.53 mg/kg; standard reperfusion) or half-dose TNK (0.27 mg/kg) plus abciximab (combination therapy), and then further randomized into two corresponding regimens of unfractionated heparin (UFA) or varying regimens of enoxaparin with and without an initial intravenous bolus:

  • Standard reperfusion (n=242): 

Active treatment: enoxaparin (1.0 mg/kg s.c. every 12 hours ± initial 30 mg i.v. bolus) (n=160)
Control treatment: UFH (bolus 60 IU/kg; infusion 12 IU/kg/h) (n=82)

  • Combination therapy (n=241):

Active treatment: enoxaparin (0.3–0.75 mg/kg s.c. every 12 hours ± initial i.v. bolus of 30 mg) (n=164)
Control treatment: UFH (bolus 40 IU/kg; infusion 7 IU/kg/h) (n=77)

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Endpoints

Primary efficacy endpoint: TIMI 3 flow at 60 minutes in the infarct related artery
Secondary efficacy endpoints: all-cause mortality, recurrent myocardial infarction
Primary safety endpoint: TIMI major hemorrhage at 30 days

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Trial participants

438 patients with STEMI presenting <6 hours from symptom onset

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Results

Efficacy outcome: With standard reperfusion, 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. Among all UFH patients, the rate of TIMI 3 flow was 50% and among enoxaparin patients it was 51%. Through 30 days, the composite endpoint of death and/or recurrent myocardial infarction occurred in the standard reperfusion group in 15.9% of patients with UFH and in 4.4% with enoxaparin. In the combination therapy group, the rates were 6.5% with UFH and 5.5% with enoxaparin. The pooled rate among all UFH patients was 11.3% and 4.9% among enoxaparin patients (p=0.01)
Safety outcome: Among patients receiving standard reperfusion, the rate of major hemorrhage with UFH was 2.4% and 1.9% with enoxaparin (pooled data for all enoxaparin groups). The rates of major hemorrhage were higher with combination therapy: 5.2% with UFH and 8.5% with enoxaparin

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Summary

Efficacy: Enoxaparin is a more effective adjunctive antithrombin therapy than UFH used either with full-dose TNK or the combination of half-dose TNK and abciximab
Safety: There was no increased risk of major bleeding with enoxaparin compared with UFH when standard perfusion is used

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Reference

Antman EA, Louwerenburg HW, Baars HF, Wesdorp JCL, Hamer B, Bassand J-P, Bigonzi F, Pisapia G, Gibson CM, Heidbuchel H, Braunwald E, Van de Werf F, for the ENTIRE-TIMI 23 Investigators. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction. Results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 trial. Circulation 2002;105:1642-1649

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Corresponding author

Elliott M. Antman, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA.
E-mail: eantman@rics.bwh.harvard.edu 

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