OBJECTIVES: Our aim was to design and evaluate a new and easily administered 
recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis 
in acute myocardial infarction (AMI) based on established pharmacokinetic data 
that improve the reperfusion success rate.
BACKGROUND: Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) 
grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. 
However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% 
indicate an obvious need for improved thrombolytic regimens.
METHODS: Pharmacokinetic simulations were performed to design a new rt-PA 
regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma 
level similar to that of the first plateau of the Neuhaus regimen. These aims 
were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg 
i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive 
comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min 
(B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a 
confirmation trial of regimen A in 254 consecutive patients was performed with 
angiographic assessment by independent investigators of patency at 90 min.
RESULTS: The comparative phase of the trial yielded, respectively, TIMI grade 3 
and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% 
(B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the 
trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At 
follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital 
mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and 
alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, 
respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 
3.5% needed blood transfusions.
CONCLUSIONS: The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI 
grade 3 patency rate of 81.1% at 90 min with no indication of an increased 
bleeding hazard; it was associated with a 1.2% overall mortality rate. These 
results are substantially better than those reported from all currently utilized 
regimens. Head to head comparison with established thrombolytic regimens in a 
large-scale randomized trial is warranted.