Circulation. 2003;108:135-142
Published online before print July 7, 2003, doi: 10.1161/01.CIR.0000081659.72985.A8
Published online before print July 7, 2003, doi: 10.1161/01.CIR.0000081659.72985.A8
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(Circulation. 2003;108:135.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From the Department of Cardiology and Uppsala Clinical Research Centre, Uppsala, Sweden (L.W., B.L.); Samu de Lille, Lille, France (P.G.); Department of Cardiology, University of Alberta, Edmonton, Canada (P.W.A.); Division of Cardiology, Duke University Medical Center, Durham, NC (C.B.G.); Department of Cardiology, Royal Victoria Hospital, Belfast, Northern Ireland (A.A.J.A.); Department of Cardiopulmology, Benjamin Franklin Medical Center, Free University of Berlin, Germany (H.R.A.); Biostatistical Centre, University of Leuven, Belgium (K.B.); Boehringer-Ingelheim, Ingelheim am Rhein, Germany (T.D.); Department of Medicine, University Central Hospital, Helsinki, Finland (M.M.); University Medical Center, Nijmegen, the Netherlands (F.V.); and Department of Cardiology, University of Leuven, Leuven, Belgium (F.V.d.W.).
Correspondence to Lars Wallentin, MD, PhD, Professor of Cardiology, Head Uppsala Clinical Research Center, Uppsala Clinical Research Center, Uppsala University Hospital, SE 751 85 Uppsala, Sweden. E-mail Lars.Wallentin{at}ucr.uu.se
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.
Key Words: myocardial infarction • fibrinolysis • hemorrhage • heparin • reperfusion
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