Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction

Abstract

Two dosing schedules of intravenous tissue plasminogen activator (t-PA) for acute myocardial infarction were compared in a multicenter trial. At 2.95 +/- 1.1 hours from onset of chest pain, 386 patients received 150 mg of intravenous t-PA. For the first 178 patients (group A), 60 mg were given in the first-hour dose and the remaining 90 mg were infused over 7 hours. In the subsequent 208 patients (group B), the first-hour dose was 1.0 mg/kg and the remaining 150 mg were given over 5 hours. At initial angiography 94 +/- 30 minutes into therapy, the infarct vessel patency was 64% in group A versus 75% in group B (p = 0.02). By final angiography with up to 4 selective contrast injections, patency was 68% versus 77%, respectively (p = 0.06). Repeat angiography at 7 to 10 days demonstrated reocclusion in 17% of group A and 13% of group B patients (p = 0.35). There was no difference in fibrinogen nadir or mean hematocrit drop between the 2 groups: 120 mg/dl and 11 points, respectively, in group A compared with 120 mg/dl and 10 points in group B. However, bleeding was reduced in group B patients as evident by a decrease in requirement for >=2 units of packed red blood cell transfusion (group A 36%, group B 27%, P = 0.05) and lower incidence of gastrointestinal bleeding (group A 12%, group B 4%, P = 0.002). To further study the importance of weight adjustment, patients were divided into 2 groups according to weight (=90 kg). According to the results, lighter weight patients had greater transfusion requirements (35% versus 20%, P = 0.006) and more frequent major bleeding episodes (16% versus 7%, P = 0.025). Thus, a higher, weight-adjusted first-hour dose of intravenous t-PA, with a shorter duration of maintenance infusion, is associated with: (1) improved infarct vessel patency; (2) more rapid recanalization; and (3) less bleeding complications without more fibrinogenolysis.