RANDOMIZED COMPARISON OF DIRECT THROMBIN INHIBITION VERSUS HEPARIN INCONJUNCTION WITH FIBRINOLYTIC THERAPY FOR ACUTE MYOCARDIAL-INFARCTION- RESULTS FROM THE GUSTO-IIB TRIAL

Objectives. We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days. Background. In a large scale trial of patients with acute coronary syn dromes, hirudin provided modest benefit compared with heparin. However , the interaction with thrombolytic agents was not specifically assess ed. Methods. Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thromboly tic therapy and randomly assigned to receive hirudin or heparin. Resul ts. A total of 2,274 patients received t-PA, and 1,015 received SK. Ba seline characteristics were balanced by antithrombin assignment. Among SK treated patients, death or reinfarction at 30 days occurred more o ften in those treated with adjunctive heparin (14.4%) rather than hiru din (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated patients, the rates were 10.9% wi th heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0 .68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between t hrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limite d to the SK treated patients. Conclusions. Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activit y after SK therapy and the potential for simulating the effects of a m ore potent fibrinolytic agent through direct antithrombin therapy. (C) 1998 by the American College of Cardiology.