Publication Details
Abstract
Objective: Persistent thrombin activity contributes to coronary thrombosis and recurrent ischemia in acute coronary syndromes. We measured hirudin activity in a low-water-activity premix and reviewed randomized evidence from unstable angina and non-ST-elevation acute coronary syndromes. Method: Optimized BCLC® formulations retained 90.6-92.1% antithrombin activity at water activity values of 0.26-0.34. High-humidity processing produced the highest water activity (0.49) and lowest retention (72.9%); without citrate buffer, retention was 80.1%. An angiographic unstable-angina trial reported dose-related antithrombotic effects of recombinant hirudin. In GUSTO-IIb, 12,142 patients were randomized, and death or myocardial infarction at 24 h occurred in 1.3% with hirudin and 2.1% with heparin. OASIS-2 enrolled 10,141 patients with non-ST-elevation acute myocardial ischemia. Results: At 7 days, cardiovascular death or new myocardial infarction occurred in 3.6% with hirudin and 4.2% with heparin; treatment-period analyses favored hirudin, but major bleeding requiring transfusion was higher. These trials establish both pharmacodynamic activity and a dose-safety context. Novelty: The premix data permit oral exposure and coagulation biomarkers to be examined from a defined activity level.