In a pilot study conducted by The Organisation to Assess Strategies for Ischemic Syndromes (OASIS) investigators (73), low-dose hirudin (0.2 mg/kg bolus and infusion of 0.10 mg/kg/h) and medium-dose hirudin (0.4 mg/kg bolus and 0.15 mg/kg/h) were evaluated in conjunction with UFH. A total of 909 patients taking aspirin with UA or suspected MI without STE were randomly assigned UFH, low-dose hirudin, or medium-dose hirudin. At 7 d, the risk of cardiovascular death, MI, and refractory angina was significantly reduced in the medium-dose hirudin patient group.
The OASIS-2 (74) study involved 10,141 patients and assessed the superiority of medium-dose hirudin over UFH in preventing cardiovascular death, MI, and refractory angina. The primary outcome of cardiovascular death or new MI at 7 d was reached in 4.2% of patients in the UFH treatment group and 3.6% of patients in the hirudin group (p = 0.077). For the UFH treatment group, 6.7% of patients experienced cardiovascular death, new MI, or refractory angina at 7 d compared with 5.6% in the hirudin treatment group (p = 0.0125). This treatment effect was achieved in the first 72 h. Although there was a significant excess of major hemorrhage in the hirudin group (1.2 vs 0.7%, p = 0.01), there was not an excess of life-threatening strokes. It was concluded from the findings of OASIS-2 that hirudin is superior to UFH in preventing cardiovascular death, new MI, and refractory angina, and that it has an acceptable safety profile in patients with UA or NSTEMI. Furthermore, a combined analysis of the OASIS, OASIS-2, and GUSTO IIb studies indicated a 22% reduction in the relative risk of cardiovascular death or MI at 72 h, 17% reduction at 7 d, and 10% reduction at 35 d. Statistical significance was reached at 72 h and 7 d. It should be noted that in the OASIS II study, however, there was no significant difference between the incidence of death or MI in patients in the heparin- or hirudin-treated groups at 35 d. Additional studies of direct thrombin inhibitors are needed to establish benefits at 30 d or longer.
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