COMPARISON OF THE EFFECTS OF 2 DOSES OF RECOMBINANT HIRUDIN COMPARED WITH HEPARIN IN PATIENTS WITH ACUTE-MYOCARDIAL-ISCHEMIA WITHOUT ST-ELEVATION - A PILOT-STUDY

Background Despite the use of aspirin and heparin, patients with acute ischemic syndromes are at risk of myocardial infarction (MI) or refra ctory ischemia. Therefore, evaluation of more potent antithrombotic th erapies is warranted. Methods and Results Patients (n=909) with unstab le angina or suspected acute MI without ST-segment elevation were rand omized to receive heparin (5000 IU bolus+1000 to 1200 U/h, n=371), low -dose hirudin (LDHir) (0.2 mg/kg bolus+0.10 mg.kg(-1).h(-1) infusion, n=271), or medium-dose hirudin (MDHir) (0.4 mg/kg bolus+0.15 mg.kg(-1) .h(-1) infusion, n=267) for 72 hours. At 7 days, 6.5% of patients in t he heparin group, 4.4% in the LDHir group, and 3.0% in the MDHir group (P=.267 heparin versus low-dose hirudin; P=.047 heparin Versus medium -dose hirudin) suffered cardiovascular death, new MI, or refractory an gina (primary outcome). The proportions with cardiovascular death, new MI, or refractory or severe angina (secondary outcome) were 15.6%, 12 .5%, and 9.4%, respectively (P=.27 for heparin versus LDHir; P=.02 for heparin Versus MDHir). The rates of new MI were 4.9%, 2.6%, and 1.9%, respectively (P=.14 heparin Versus LDHir; P=.046 heparin versus MDHir ). Fewer patients underwent coronary artery bypass graft surgery in th e two hirudin groups (3.7% low-dose, 1.1% medium-dose group) compared with heparin (4.0%) (P=.028 for heparin versus MDHir). After cessation of study treatments, there was an increase in ischemic events in the LDHir group at approximate to 24 hours and at approximate to 5 days in the medium-dose group. Nevertheless, at 180 days, the differences bet ween hirudin and heparin persisted. Conclusions Hirudin, especially at the medium dose, appears to be superior to heparin in preventing isch emic outcomes in unstable angina or acute MI without ST elevation.