July 8, 2003Open Access
View Full PaperEfficacy and Safety of Tenecteplase in Combination With the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting
Key Result
Prehospital tenecteplase plus enoxaparin tended to reduce 30-day mortality, reinfarction, or refractory ischemia compared to UFH (14.2% vs 17.4%, P=0.080), but increased intracranial hemorrhage.
Study Design
Type
RCT (n=1,639)
Structured PICO
Does tenecteplase combined with enoxaparin reduce 30-day mortality, reinfarction, or refractory ischemia compared to tenecteplase with unfractionated heparin in prehospital STEMI patients?
P
Population
1,639 patients with ST-elevation myocardial infarction treated in the prehospital setting and followed for 30 days.
I
Intervention
Tenecteplase combined with intravenous bolus of 30 mg enoxaparin followed by 1 mg/kg subcutaneously BID for a maximum of 7 days
C
Comparator
Tenecteplase combined with weight-adjusted unfractionated heparin (UFH) for 48 hours
O
Outcome
Composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemiacomposite
In prehospital STEMI patients receiving tenecteplase, enoxaparin reduced early ischemic events compared to UFH but increased intracranial hemorrhage, leading to the continued recommendation of UFH as routine therapy.
Main Result
Absolute Event Rate: 14.2% vs 17.4%
p-value: p=0.080
Limitations
- Lower doses of enoxaparin need to be tested in elderly patients due to an increase in intracranial hemorrhage in patients >75 years of age.
Abstract
BACKGROUND: The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P=0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P=0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P=0.028) and refractory ischemia (4.4% versus 6.5%, P=0.067) but increases in total stroke (2.9% versus 1.3%, P=0.026) and intracranial hemorrhage (2.20% versus 0.97%, P=0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age. CONCLUSIONS: Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.
Cite This Study
Wallentin et al. (Tue,) conducted a rct in ST-elevation myocardial infarction (n=1,639). Tenecteplase plus Enoxaparin vs. Tenecteplase plus Unfractionated Heparin (UFH) was evaluated on Composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia (p=0.080). Prehospital tenecteplase plus enoxaparin tended to reduce 30-day mortality, reinfarction, or refractory ischemia compared to UFH (14.2% vs 17.4%, P=0.080), but increased intracranial hemorrhage.