Enoxaparin versus unfractionated heparin as antithrombin therapy in patients receiving fibrinolysis for ST-elevation myocardial infarction : Design and rationale for the enoxaparin and thrombolysis reperfusion for acute myocardial infarction treatment-thrombolysis in myocardial infarction study 25 (ExTRACT-TIMI 25)

Even after treatment with fibrinolytics, aspirin (ASA), and intravenous unfractionated heparin (UFH) in contemporary phase 3 trials of pharmacological reperfusion therapy for STEMI, there is still at least a 10% rate of death or reinfarction 1 month after treatment.4-10 This limitation is mainly caused by a combination of failure to achieve an early, sustained, complete antegrade flow in the infarct-related artery and reocclusion after an initially successful fibrinolysis.11,12 The risk of reocclusion is related to the underlying degree of stenosis as well as to the residual thrombus.13-15 When reocclusion occurs, it may be associated with recurrent infarction and an increased risk of mortality, morbidity, and poor ventricular function.16 An additional limitation of fibrinolytic therapy is the risk of intracranial hemorrhage (ICH), especially in elderly patients.5-10,17,18 The risk of ICH, at least in part, is considered to be related to the antithrombotic therapy that is commonly prescribed in conjunction with fibrinolytics and has been reported not only for UFH but also for direct thrombin inhibitors and low-molecular-weight heparins.6-8,18-20 Enoxaparin has been evaluated as an antithrombin to support fibrinolysis in at least 7 trials spanning all the major fibrinolytics in common clinical use with the exception of reteplase.19-25 In all the trials, the control arm was UFH, except for the AMI-SK trial in which it was placebo. [...]a generally consistent theme of higher rates of ST-segment resolution and a lower rate of reocclusion of the infarct artery, reinfarction, or recurrent ischemic events has been observed in patients receiving enoxaparin regardless of whether the control group used placebo or UFH.2 The most comprehensive data available are from the ASSENT-3 trial where patients received tenecteplase and either UFH (bolus 60 U/kg, initial infusion 12 U/kg/h, duration of treatment 48 hours) or enoxaparin (bolus 30 mg, subcutaneous injections 1.0 mg/kg every 12 hours for the duration of hospital stay).19 Each of the elements of the composite end point of 30-day mortality, inhospital reinfarction, or inhospital recurrent ischemia was reduced with enoxaparin compared with UFH.