Hirulog in the Treatment of Unstable Angina

Publisher Website
Google Scholar
Abstract
BackgroundDirect thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin.Methods and ResultsTIMI 7 was a randomized, double-blind study of Hirulog, given with 325 mg/d aspirin to 410 patients with unstable angina. Patients received a constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n=160), 0.25 (n=81), 0.5 (n=88), and 1.0 (n=81) mg · kg−1· h−1. The primary efficacy end point was “unsatisfactory outcome,” defined as death, nonfatal myocardial infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest with ECG changes by 72 hours. Unsatisfactory outcome was not different among the four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (P=NS). However, the secondary end point of death or nonfatal MI through hospital discharge occurred in 10.0% of patients treated with 0.02 mg · kg−1· h−1compared with 3.2% of patients treated with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg · kg−1· h−1,P=.008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to Hirulog.ConclusionsThe direct thrombin inhibitor Hirulog is a promising new antithrombotic agent that deserves further study. The results of TIMI 7 lend support to the use of an antithrombin agent with aspirin in patients with unstable angina.