Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction

Circulation. 2003 Jul 15;108(2):135-42. doi: 10.1161/01.CIR.0000081659.72985.A8. Epub 2003 Jul 7.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Drug Therapy, Combination
  • Emergency Medical Services / methods*
  • Emergency Medical Services / statistics & numerical data
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use*
  • Female
  • Hemorrhage / etiology
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Risk
  • Safety
  • Survival Analysis
  • Tenecteplase
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods*
  • Time Factors
  • Tissue Plasminogen Activator / adverse effects
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome

Substances

  • Enoxaparin
  • Heparin
  • Tissue Plasminogen Activator
  • Tenecteplase