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

Eric J. Topol, Barry S. George, Dean J. Kereiakes, Richard J. Candela, Charles W. Abbottsmith, David C. Stump, Jane M. Boswick, Richard S. Stack, Robert M. Califf

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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 versus ≥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.

Original languageEnglish (US)
Pages (from-to)723-728
Number of pages6
JournalThe American Journal of Cardiology
Volume61
Issue number10
DOIs
StatePublished - Apr 1 1988

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Topol, E. J., George, B. S., Kereiakes, D. J., Candela, R. J., Abbottsmith, C. W., Stump, D. C., Boswick, J. M., Stack, R. S., & Califf, R. M. (1988). Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction. The American Journal of Cardiology, 61(10), 723-728. https://doi.org/10.1016/0002-9149(88)91055-7