Effects of recombinant hirudin (lepirudin) compared with heparin on death,myocardial infarction, refractory angina, and revascularisation proceduresin patients with acute myocardial ischaemia without ST elevation: a randomised trial

Background Despite the use of heparin and aspirin, 5-10% of patients with u nstable angina develop myocardial infarction or refractory angina in hospit al. We tested the hypothesis that recombinant hirudin (lepirudin), a direct thrombin inhibitor, would be superior to heparin, an indirect thrombin inh ibitor, in patients with acute ischaemic syndromes who were receiving aspir in. Methods 10141 patients with unstable angina or suspected acute myocardial i nfarction without ST elevation were randomly assigned heparin (5000 units b olus then 15 units kg(-1) h(-1); n = 5058) or hirudin (0.4 mg/kg bolus then 0.15 mg kg(-1) h(-1) infusion; n = 5083) for 72 h in a double-blind trial. The primary outcome measure was cardiovascular death or new myocardial inf arction at 7 days. Analysis was by intention to treat. Findings At 7 days, 213 (4.2%) patients in the heparin group and 182 (3.6%) in the hirudin group had experienced cardiovascular death or new myocardia l infarction (relative risk 0.84 [95% CI 0.69-1.02]; p = 0.077). The number s with cardiovascular death, new myocardial infarction, or refractory angin a at 7 days were 340 (6.7%) with heparin and 284 (5.6%) with hirudin (0.82 [0.70-0.96]; p = 0.0125). These differences were primarily observed during the 72 h treatment period (cardiovascular death or myocardial infarction re lative risk 0.76 [0.59-0.99], p = 0.039: cardiovascular death, myocardial i nfarction, or refractory angina 0.78 [0.63-0.96], p = 0.019). Although ther e was an excess of major bleeding requiring transfusion with hirudin (59 [1 .2%] vs 34 [0.7%] with heparin; p = 0.01), there was no excess in life-thre atening episodes (20 in each group) or strokes (14 in each group). Interpretation The data from OASIS-2 suggest that recombinant hirudin is su perior to heparin in preventing cardiovascular death, myocardial infarction , and refractory angina with an acceptable safety profile in patients with unstable angina or acute myocardial infarction without ST elevation. Thus, a direct thrombin inhibitor is more effective than an indirect thrombin inh ibitor.