Comparison of the effects of two doses of recombinant hirudin compared with heparin in patients with acute myocardial ischemia without ST elevation: a pilot study. Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators.

Abstract

Despite the use of aspirin and heparin, patients with acute ischemic syndromes are at risk of myocardial infarction (MI) or refractory ischemia. Therefore, evaluation of more potent antithrombotic therapies is warranted. Patients (n=909) with unstable angina or suspected acute MI without ST-segment elevation were randomized 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 x kg(-1) x h(-1) infusion, n=271), or medium-dose hirudin (MDHir) (0.4 mg/kg bolus+0.15 mg x kg(-1) x h(-1) infusion, n=267) for 72 hours. At 7 days, 6.5% of patients in the 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 angina (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 the 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 approximately 24 hours and at approximately 5 days in the medium-dose group. Nevertheless, at 180 days, the differences between hirudin and heparin persisted. Hirudin, especially at the medium dose, appears to be superior to heparin in preventing ischemic outcomes in unstable angina or acute MI without ST elevation.