COMPARISON OF FRONT-LOADED RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR, ANISTREPLASE AND COMBINATION THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL-INFARCTION - RESULTS OF THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION (TIMI) 4 TRIAL

Objectives. The aim of our study was to determine a superior thrombolytic regimen from three: anistreplase (APSAC), front-loaded recombinant tissue-type plasminogen activator (rt-PA) or combination thrombolytic therapy. Background. Although thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction, it has not been clear whether more aggressive thrombolytic-antithrombotic regimens could improve the outcome achieved with standard regimens. Methods. To address this issue, 382 patients with acute myocardial infarction were randomized to receive in a double blind fashion (along with intravenous heparin and aspirin) APSAC, front-loaded rt-PA or a combination of both agents. The primary end point ''unsatisfactory outcome'' was a composite clinical end point assessed through hospital discharge. Results. Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) at 60 min after the start of thrombolysis was significantly higher in rt-PA-treated patients (77.8% vs. 59.5% for APSAC treated patients and 59.3% for combination-treated patients [rt-PA vs. APSAC, p = 0.02; rt-PA vs, combination, p = 0.03]). At 90 min, the incidence of both infarct-related artery patency and TIMI grade 3 flow was significantly higher in rt-PA-treated patients (60.2% had TIMI grade 3 how vs. 42.9% and 44.8% of APSAC- and combination-treated patients, respectively [rt-PA vs. APSAC, p < 0.01; rt-PA vs. combination, p = 0.02]). The incidence of unsatisfactory outcome was 41.3% for rt-PA compared with 49% for APSAC and 53.6% for the combination (rt-PA vs. APSAC, p = 0.19; rt PA vs. combination, p = 0.06). The mortality rate at 6 weeks was lowest in the rt-PA-treated patients (2.2% vs. 8.8% for APSAC and 7.2% for combination thrombolytic therapy [rt-PA vs. APSAC, p = 0.02; rt-PA vs, combination, p = 0.06]). Conclusions. Front-loaded rt-PA achieved significantly higher rates of early reperfusion and was associated with trends toward better overall clinical benefit and survival than those achieved with a standard thrombolytic agent or combination thrombolytic therapy. These findings support the concept that more rapid reperfusion of the infarct related artery is associated with improved clinical outcome.