A Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary Syndromes

Abstract

Background Thrombin has a pivotal role in the pathogenesis of acute coronary thrombosis. We compared the clinical efficacy of a potent, direct thrombin inhibitor, recombinant hirudin, with that of heparin (an indirect antithrombin agent) in patients with unstable angina or acute myocardial infarction. Methods At 373 hospitals in 13 countries, 12,142 patients with acute coronary syndromes were ran- domly assigned to 72 hours of therapy with either in- travenous heparin or hirudin. Patients were stratified according to the presence of ST-segment elevation on the base-line electrocardiogram (4131 patients) or its absence (8011 patients), with the latter character- istic considered to indicate unstable angina or non– Q-wave myocardial infarction. Results At 24 hours, the risk of death or myocar- dial infarction was significantly lower in the group assigned to hirudin therapy than in the group assigned to heparin (1.3 percent vs. 2.1 percent, P ? 0.001). The primary end point of death or nonfa- tal myocardial infarction or reinfarction at 30 days was reached in 9.8 percent of the heparin group as compared with 8.9 percent of the hirudin group (odds ratio for the risk of the end point in the hirudin group, 0.89; 95 percent confidence interval, 0.79 to 1.00; P ? 0.06). The predominant effect of hirudin was on myocardial infarction or reinfarction and was not influenced by ST-segment status. There were no significant differences in the incidence of serious or life-threatening bleeding complications, but hirudin therapy was associated with a higher incidence of moderate bleeding (8.8 percent vs. 7.7 percent, P ? 0.03). Conclusions For acute coronary syndromes, re- combinant hirudin provided a small advantage, as compared with heparin, principally related to a re- duction in the risk of nonfatal myocardial infarction. The relative therapeutic effect was more pronounced early (at 24 hours) but dissipated over time. The small benefit was consistent across the spectrum of acute coronary syndromes and was not associated with a greater risk of major bleeding complications.