Background: The Thrombolysis in Myocardial Infarction (TIMI) 8 trial was undertaken to compare the efficacy and safety of bivalirudin versus unfractionated heparin in a double-blind phase III trial of patients with unstable angina/non-ST-elevation myocardial infarction (MI).
Methods: All patients received aspirin and were randomized either to unfractionated heparin (bolus of 70 U/kg followed by an infusion of 15 U/kg/h) or bivalirudin (bolus of 0.1 mg/kg followed by an infusion of 0.25 mg/kg/h) for a minimum of 72 hours. The primary efficacy end point was a composite of all cause mortality or nonfatal recurrent MI.
Results: A total of 133 of the planned 5320 patients were enrolled, at which point the study was terminated by the sponsor because of a decision at the time to suspend further development of bivalirudin. Through 14 days, the incidence of death or nonfatal MI was 9.2% in the 65 patients in the unfractionated heparin group and was 2.9% in the 68 patients in the bivalirudin group, odds ratio (95% CI) 0.30 (0.06-1.53). Major hemorrhage occurred in 3 patients in the unfractionated heparin group (4.6%) but in none of the patients in the bivalirudin group (P =.11).
Conclusions: The trend toward a lower rate of death or nonfatal MI in the bivalirudin group is consistent with a therapeutic effect of the drug and is consistent with other trials of bivalirudin in patients with acute coronary syndromes. The potential for clinically meaningful antithrombotic activity without an increased risk of bleeding and availablility of an alternative anticoagulation strategy in patients who cannot tolerate unfractionated heparin are particularly attractive and underscore the need for further evaluation of bivalirudin.