A randomized trial confirming the efficacy of reduced dose recombinant tissue plasminogen activator in a Chinese myocardial infarction population and demonstrating superiority to usual dose urokinase: The TUCC trial

Background Reports from Japan suggest effective myocardial infarction (MI) treatment in Asian patients with much lower doses of tissue plasminogen activators (tPA) than used in European and American regimens. Because increasing doses of fibrinolytics lead to increased bleeding complications, identification of patients who respond to reduced doses is of importance. We conducted a trial in the People's Republic of China in which reduced-dose recombinant tPA was compared with the standard local therapy, urokinase. Methods Four hundred patients with acute MI within 12 hours of symptom onset were to be randomized to an 8-mg bolus of recombinant tPA followed by a 42-mg 90-minute infusion or 1.5 million units of urokinase as a 30-minute infusion. Patients received aspirin and heparin and underwent angiography to determine infarct artery potency 90 minutes after the start of therapy. Results The Data and Safety Monitoring Board recommended premature termination after 342 patients were recruited. Infarct artery potency (grade 2 or 3) occurred in 79% of patients receiving recombinant tPA and in 53% of patients receiving urokinase (P<.001); Thombolysis in Myocardial Infarction (TIMI) grade 3 flow was 48% and 28%, respectively (P<.001). The higher-patency-rate recombinant tPA growth had better posttreatment left ventricular ejection fractions, 58.6% versus 54.7%, P<.01. Adverse events were infrequent and not significantly different in the 2 groups. Conclusions This study confirms that a substantially lower dose of recombinant tPA is effective in Asian patients compared with that required in Western patients even after consideration of body weight. Specific dose-response studies should be performed with fibrinolytic regimens to avoid overdosage with its attendant risks of excess bleeding.