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

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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27366/1/0000392.pd

Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction

: Little attention has been paid to the importance of clinical factors associated with bleeding complications caused by the use of thrombolytic agents. The goal of our study was to examine clinical and hematologic factors associated with an increased risk of bleeding in a prospectively observed population that received intravenous tissue plasminogen activator for acute myocardial infarction.: Bleeding complications were evaluated in 386 consecutive patients treated with 150 mg of tissue plasminogen activator over six to eight hours for acute myocardial infarction. All patients also underwent immediate cardiac catheterization.: Quantitation of blood loss during the patients' hospital stay included a median drop in hematocrit of 11.4 points, a median nadir hematocrit of 31.2, a 14 percent rate of significant clinically evident bleeding, and a 31 percent rate of transfusion of two or more units of blood. All of these parameters were much more severe in patients treated with coronary artery bypass surgery. Access site hematoma was the most common source of bleeding (45 percent of patients), whereas 8 percent had gastrointestinal bleeding, two patients had retroperitoneal bleeding, and two patients had intracranial bleeding. The median nadir fibrinogen was 1.3 g/liter. Multiple linear regression models were used to investigate the relationship between clinical variables, including multiple hematologic measurements, and measures of the amount of blood loss. The use of coronary artery bypass grafting was the variable most closely associated with hemorrhage. Other invasive procedures (angioplasty and intra-aortic balloon pumping) were also associated with increased bleeding. Among the patient descriptors examined, lighter weight, older age, female sex, and history of hypertension were associated with greater blood loss. Of laboratory coagulation parameters, only nadir fibrinogen levels were significantly associated with more bleeding.: Careful clinical evaluation may improve assessment of the risk/benefit ratio of thrombolytic therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27546/1/0000590.pd