Front-loaded rt-PA achieved higher early reperfusion rates and lower 6-week mortality (2.2% vs 8.8%, p=0.02) compared to APSAC, with a trend toward fewer unsatisfactory outcomes (41.3% vs 49%).
RCT (n=382)
Double-blind
randomized
Does front-loaded rt-PA or combination thrombolytic therapy improve clinical outcomes compared to anistreplase in patients with acute myocardial infarction?
Front-loaded rt-PA achieves significantly higher rates of early reperfusion and lower 6-week mortality compared to anistreplase or combination therapy in patients with acute myocardial infarction.
Absolute Event Rate: 41.3% vs 49%
p-value: p=0.19
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 flow 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.
Cannon et al. (1994) conducted an RCT in acute myocardial infarction (n=382). front-loaded recombinant tissue-type plasminogen activator (rt-PA) vs. anistreplase (APSAC) or combination therapy was evaluated on unsatisfactory outcome (composite clinical end point assessed through hospital discharge) (p=0.19). Front-loaded rt-PA achieved higher early reperfusion rates and lower 6-week mortality (2.2% vs 8.8%, p=0.02) compared to APSAC, with a trend toward fewer unsatisfactory outcomes (41.3% vs 49%).