Thrombolysis in myocardial infarction (TIMI): comparative studies of coronary reperfusion and systemic fibrinogenolysis with two forms of recombinant tissue-type plasminogen activator.
Coronary recanalization rates and changes in plasma proteins of the fibrinolytic system were evaluated with two preparations of recombinant tissue-type plasminogen activator (rt-PA): the early formulation in liquid excipient ("old" rt-PA) and the later lyophilized form ("new" rt-PA). The dose dependency of coronary recanalization and of effects on plasma proteins was evaluated for the new rt-PA. Four groups of patients were studied: Study 1, 80 mg old rt-PA infused intravenously over 3 hours (n = 113); Study A, 80 mg new rt-PA over 3 hours (n = 47); Study B, 100 mg new rt-PA over 3 hours (n = 83); and Study C, 150 mg new rt-PA over 6 hours (n = 62). With equal doses of 80 mg, coronary recanalization rates at 90 minutes of infusion, determined angiographically, averaged 62% (Study 1) and 45% (Study A) with no overlap of 95% confidence limits. Increasing the dose of the new rt-PA to 100 mg, recanalization rates at 90 minutes averaged 71% (Study B), similar to those observed in Study 1. An increase to 150 mg resulted in higher recanalization rates at 30 minutes of infusion, 42% compared with 24% in Study 1 with no overlap of 95% confidence limits, and comparable rates at 90 minutes, 76 versus 62%. A linear trend test indicated a significant relation (p less than 0.01) between the dose of the new rt-PA and the rate of coronary recanalization at 30, 60 and 90 minutes of infusion. The new rt-PA affected plasma proteins of the fibrinolytic system less than the old form. There was a dose-dependent relation (p less than 0.001) in the effect of the new rt-PA on the plasma proteins. The frequency of bleeding complications was similar in the four study groups. These results indicate that the new rt-PA is less potent than the old rt-PA, in relation to both coronary reperfusion and systemic fibrinogenolysis. A higher and longer dosage regimen caused more rapid recanalization with similar effects on fibrinogenolysis.
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator