Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin

Am Heart J. 2002 Sep;144(3):470-7. doi: 10.1067/mhj.2002.126115.

Abstract

Background: In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding.

Objective: Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA.

Methods: Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days.

Results: The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively).

Conclusions: Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Coronary Disease / diagnosis
  • Coronary Disease / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Electrocardiography / statistics & numerical data*
  • Enoxaparin / therapeutic use*
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Hemorrhage / chemically induced*
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Platelet Glycoprotein GPIIb-IIIa Complex / adverse effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / therapeutic use*
  • Tirofiban
  • Treatment Outcome
  • Tyrosine / adverse effects
  • Tyrosine / analogs & derivatives*
  • Tyrosine / therapeutic use*

Substances

  • Enoxaparin
  • Fibrinolytic Agents
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tyrosine
  • Heparin
  • Tirofiban
  • Aspirin