Treatment of Enoxaparin and Tirofiban in Acute Myocardial Infarction - TETAMI

Description:

Randomized trial comparing: 1) enoxaparin with unfractionated heparin (UFH), and 2) tirofiban with placebo for treatment of acute myocardial infarction (MI) patients not eligible for reperfusion.

Hypothesis:

In acute MI patients not eligible for reperfusion, treatment with enoxaparin will result in improved 30-day outcomes compared with UFH treatment. A second hypothesis compared the effect of tirofiban with placebo on 30-day events.

Study Design

Study Design:

Patients Enrolled: 1,224.
Mean Follow Up: 30 days.
Mean Patient Age: mean age 63 years
Female: 28

Patient Populations:

ST elevation MI <24 hours; not eligible for reperfusion therapy.

Exclusions:

Killip class IV.

Primary Endpoints:

Composite 30-day events (death, MI, recurrent angina).

Secondary Endpoints:

Individual endpoints of composite 30-day events (death, MI, recurrent angina).

Drug/Procedures Used:

1) Enoxaparin, 30 mg IV bolus + 1 mg/kg SC for 2-8 days + tirofiban, 10 microgram/kg IV bolus + 0.10 microgram/kg/min IV infusion 2) enoxaparin (above dose) + placebo, 3) UFH + tirofiban (above dose), and 4) UFH + placebo.

Concomitant Medications:

Aspirin.

Principal Findings:

28% of patients enrolled in the trial had already received pretreatment with UFH at the time of enrollment. Time from symptom onset to treatment was 16 to 17 hours, and >75% of patients presented >12 hours from symptom onset. The rate of 30-day composite endpoint of death, MI, or recurrent angina did not differ between the enoxaparin group (15.7%) and the UFH group (17.3%, p=0.471). No differences were seen with the individual endpoints that made up the composite. Additionally, the composite endpoint did not differ between the tirofiban group (16.6%) and the placebo group (16.4%, p=0.8), nor did the individual endpoints. There was no significant difference in either analysis with regard to thrombolysis in myocardial infarction (TIMI) major bleed (1.5% enoxaparin vs 1.3% UFH, p=NS; 1.8% tirofiban, 1.0% placebo, p=NS).

Interpretation:

Approximately 15-30% of patients who present with acute MI are not eligible to receive reperfusion therapy. The current ACC/AHA guidelines recommend patients presenting too late for reperfusion therapy be treated with aspirin and UFH, but have no recommendation for low molecular weight heparins in these patients. The present trial showed that treatment with enoxaparin did not provide added benefit to treatment with UFH. Additionally, treatment with the glycoprotein (GP) IIb/IIIa inhibitor tirofiban did not provide additional benefit to aspirin. The study was powered to detect a 30% treatment effect given a 25% event rate. The event rate in the trial was actually much lower at 16%, indicating the trial may have been underpowered to detect a difference.

References:

Cohen M, et al. The Safety and Efficacy of Subcutaneous Enoxaparin Versus Intravenous Unfractionated Heparin and Tirofiban Versus Placebo in the Treatment of Acute ST-Segment Elevation Myocardial Infarction Patients Ineligible for Reperfusion (TETAMI). J Am Coll Cardiol 2003;42:1348-56.

Presented at AHA 2002, late breaking clinical trials.

Clinical Topics: Anticoagulation Management

Keywords: Myocardial Infarction, Platelet Aggregation Inhibitors, Enoxaparin, Heparin, Low-Molecular-Weight, Fibrinolytic Agents, Platelet Glycoprotein GPIIb-IIIa Complex


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