Bleeding with direct thrombin inhibitors

The active substance in bivalirudin (Hirulog), a direct thrombin inhibitor, is a 20-amino acids ynthetic peptide based on the hirudin template. In the Hirulog angioplasty study, 4098 patients with unstable or post infarction angina were randomized to bivalirudin or heparin before PTCA (14). The conclusion of this study was that there was no difference in the 30-day primary endpoint with either treatment. Patients randomized to Hirulog, however, did have a statistically significant reduced incidence of bleeding-related complications. 

The HERO-2 trial evaluated the efficacy of another direct thrombin inhibitor, bivalirudin, versus UFH in conjunction with streptokinase (39). Bivalirudin did not reduce mortality compared with UFH but was associated with a lower rate of recurrent MI within 96 hours (1.6% vs. 2.3% p = 0.005). Severe bleeding occurred in 0.7% of the bivalirudin group versus 0.5% for heparin (p = 0.07), and intracerebral bleeding occurred in 0.6% versus 0.4% (p = 0.09), respectively, possibly related to higher aPPT levels in the bivalirudin group. The frequency of moderate and mild bleeding was also greater with bivalirudin. 

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