ExTRACT-TIMI 25 Fibrinolytic Study - ExTRACT-TIMI 25 Fibrinolytic Study


The goal of the study was to compare the effect of treatment with enoxaparin compared with unfractionated heparin (UFH) on mortality and recurrent myocardial infarction among ST-elevation myocardial infarction (STEMI) patients receiving fibrinolysis with a fibrin-specific agent or streptokinase (SK).

Study Design

Study Design:

Patients Enrolled: 20,479
Mean Follow Up: 30 days

Patient Populations:

Male or nonpregnant female over 18 years old presenting within 6 hours of the onset of ischemic symptoms of STEMI (0.1 mV in two or more limb leads or 0.2 mV in two or more contiguous precordial leads or left bundle branch block), scheduled to undergo fibrinolysis


Patients who were ineligible to receive thrombolytics were excluded. Other exclusions: serum creatine >2.5 (men) or creatine >2.0 (women), recent/current exposure to low molecular weight heparin or glycoprotein IIb/IIIa inhibitors, international normalized ratio >1.5.

Primary Endpoints:

All-cause mortality or nonfatal recurrent MI through 30 days

Secondary Endpoints:

Composite of all-cause mortality, nonfatal reinfarction, or recurrent myocardial ischemia leading to urgent revascularization in the first 30 days

Drug/Procedures Used:

Patients were randomized in a double-blind, double-dummy manner to enoxaparin or UFH. The choice of thrombolytic was determined by the treating physician. UFH or placebo was given as an intravenous (IV) bolus of 60 U/kg followed by a continuous infusion at 12 U/kg/h, adjusting the rate to maintain an activated partial thromboplastin time of 1.5-2.0 times normal. Enoxaparin was administered as a 30 mg IV bolus followed by 1 mg/kg subcutaneous (SC) injections every 12 hours. For patients 75 years and older or with impaired renal function (creatinine clearance <30 ml/min), IV bolus was omitted and 0.75 mg/kg SC injections were used. The subcutaneous enoxaparin regimen was continued until hospital discharge or for a maximum of 8 days.

Principal Findings:

Overall, 16,283 (79.7%) patients were treated with fibrin-specific lytics and 4,139 (20.3%) received SK. Of the patients who received fibrin-specific agents, 11,175 (68.6%) were treated with alteplase, 3,986 (24.5%) with tenecteplase, and 1,122 (6.9%) with reteplase. Patients who received SK were older (14.9% vs. 11.7% were older than 75), had a higher prevalence of diabetes (16.4% vs. 14.8%), and were less likely to be a smoker (42.4 vs. 48.6%). In-hospital medical therapy was similar in both cohorts. The majority of patients in both groups received aspirin (95.2%), beta-blockers (85.8%), and inhibitors of the renin-angiotensin system (79.7%).

The primary endpoint 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 treated with fibrin-specific lytics (adjusted odds ratio [ORadj], 0.78; 95% confidence interval [CI], 0.70-0.87; P < 0.001) and 11.8% versus 10.2% treated with SK (ORadj, 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 nonsignificant (p = 0.20). Death, nonfatal MI, or major bleeding was significantly reduced with enoxaparin in the fibrin-specific cohort (ORadj, 0.82; 95% CI, 0.74-0.91; p < 0.001) and favored enoxaparin in the SK cohort (ORadj, 0.89; 95% CI, 0.72-1.10; p = 0.29; P interaction = 0.53).


Among patients receiving thrombolysis for STEMI, treatment with enoxaparin was associated with a reduction in the primary endpoint of death or nonfatal recurrent MI compared with UFH. This reduction was seen regardless of choice of lytic. Although major bleeding was higher in patients from both lytic cohorts who received enoxaparin, all composite net clinical benefit endpoints favored enoxaparin regardless of the lytic prescribed.

This study is a substudy analysis of the ExTRACT TIMI-25 study, which demonstrated the superiority of enoxaparin in STEMI patients receiving thrombolysis. In the current analysis, the authors showed that enoxaparin is preferable to UFH regardless of which lytic was used. Limitations include the nonrandomized nature of the fibrinolytic therapy administered to the patient, which could confound data. The study was not powered to detect differences among the different lytic cohorts.


Presented by Dr. Roberto Giraldez at the American Heart Association Annual Scientific Sessions, Chicago, IL, November 2006.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, EP Basic Science, Lipid Metabolism

Keywords: Thrombolytic Therapy, Odds Ratio, Myocardial Infarction, Heparin, Renin-Angiotensin System, Creatinine, Intracranial Hemorrhages, Streptokinase, Enoxaparin, Fibrinolysis, Partial Thromboplastin Time, Bundle-Branch Block, Confidence Intervals, Tissue Plasminogen Activator, Diabetes Mellitus

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