(Circulation. 1997;96:769-777.)
© 1997 American Heart Association, Inc.
Articles |
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
Correspondence to Dr Salim Yusuf, Division of Cardiology, McMaster University, Hamilton General Hospital, 237 Barton St E, Hamilton, Ontario L8L 2X2, Canada. E-mail yusufs{at}fhs.csu.mcmaster.ca
Background 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.
Methods and Results 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·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 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 
24 hours and at 5
days in the medium-dose group. Nevertheless, at 180 days, the
differences between hirudin and heparin persisted.
Conclusions 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.
Key Words: angina • hirudin • heparin • myocardial infarction
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