ExTRACT-TIMI 25

Enoxaparin and Thrombolysis Reperfusion for Acute myocardial infarction Treatment – Thrombolysis In Myocardial Infarction 25 (2006)

Condition

Prevention of reocclusion after successful fibrinolysis in patients with ST-elevation myocardial infarction (STEMI)

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Objective

To compare enoxaparin and unfractionated heparin as adjunctive therapy for fibrinolysis in patients with STEMI

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Trial design

Randomized double-blind, parallel-group study with double-dummy design
Active treatment: enoxaparin, dosing according to the patients age:

  • patients <70 years: 30 mg i.v. bolus, then 1.0 mg/kg s.c. every 12 hours (maximum of 100 mg for the first two injections)´
  • patients ≥75 years: no bolus, 0.75 mg/kg s.c. every 12 hours (maximum of 75 mg for the first two injections)

until discharge or maximum 8 days; matching placebo (n=10,256)
Control treatment: weight-based UFH: 60 IU/kg i.v. bolus to maximum 4000 IU, then 12 IU/kg/h i.v. to maximum 1000 IU/h for at least 48 hours; matching placebo (n=10,223)

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Endpoints

Primary endpoint: composite of death from any cause or non-fatal recurrent myocardial infarction in the first 30 days after randomization
Secondary endpoints: (1) composite of death, non-fatal reinfarction, or recurrent myocardial ischemia leading to urgent revascularization in the first 30 days; (2) composite of death, non-fatal reinfarction, or non-fatal intracranial hemorrhage (net clinical benefit)

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Trial participants

20,506 patients with STEMI infarction who were scheduled to undergo fibrinolysis with streptokinase, tenecteplase, alteplase, or reteplase

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Results

Efficacy outcome: At 30 days primary outcome events (death or non-fatal myocardial infarction) had occurred in 12.0% of patients in the UFH group and in 9% of those treated with enoxaparin (relative risk reduction 17%). The mortality rate was 7.5% in the UFH group, as compared to 6.9% in the enoxaparin group. Enoxaparin significantly reduced the rate of recurrent non-fatal myocardial infarction (3.0% vs. 4.5% with UFH; relative risk reduction 33%) and the incidence of the main secondary end point of death, non-fatal myocardial infarction, or urgent revascularization (11.7% vs. 14.5%). The composite of death, non-fatal reinfarction, or non-fatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2% of patients given UFH and in 10.1% of those given enoxaparin
Safety outcome: The rates of major bleeding (including intracranial hemorrhage) at 30 days were 1.4% in the UFH group and 2.1% in the enoxaparin group (increase in relative risk 53%). Minor bleeding occurred in 1.8% and 2.6%, respectively

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Summary

Efficacy: In patients receiving fibrinolysis for STEMI, treatment with enoxaparin throughout the index hospitalization was superior to treatment with UFH for 48 hours in preventing reocclusion
Safety: Treatment with enoxaparin was associated with a significant increase in major bleedings

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Reference

Antman EM, Morrow DA, McCabe CH, Murphy SA, Ruda M, Sadowski Z, Budaj A, López-Sendón JL, Guneri S, Jiang F, White HD, Fox KAA, Braunwald E, for the ExTRACT-TIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 2006;354(15):1477-1488

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Corresponding author

Elliot M. Antman, MD, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, e-mail: 
eantman@rics.bwh.harvard.edu 

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