DOSE-RELATED EFFICACY AND BLEEDING COMPLICATIONS OF DOUBLE-CHAIN TISSUE PLASMINOGEN-ACTIVATOR IN ACUTE MYOCARDIAL-INFARCTION

Although the efficacy of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction has been demonstrated, little formal dose-ranging information is available. This study examined the use of duteplase, the double-chain rt-PA subsequently used in the Thir d international Study of Infarct Survival, in a multicenter trial of 2 67 patients with evolving acute myocardial infarction assigned to rece ive IL of 6 weight-adjusted doses. The primary and point was infarct v essel patency after 90 minutes of drug infusion. Patency was defined a s Thrombolysis in Myocardial infarction trial grade 2 or 3 perfusion, and was determined by an independent core laboratory masked to treatme nt assignment. Patency was present in 48% of patients receiving the lo west dose range and 78% of those receiving the highest, with an associ ation between thrombolytic dose and patency (p = 0.009). The frequency of serious bleeding complications also correlated with the total dose of rt(PA infused (p = 0.003). Bleeding complications were primarily r elated to instrumentation; blood loss requiring transfusion or otherwi se deemed clinically significant occurred in 12% of patients (central nervous system hemorrhage occurred in 1.1%). Thus, higher doses of rt- PA are associated both with increased efficacy and increased risk of s erious bleeding complications. weight-adjusted dosing may provide an o ptimal risk-benefit ratio for thrombolysis during acute myocardial inf arction.