Sixty-Minute Alteplase Protocol: New Accelerated Recombinant Tissue-Type Plasminogen Activator Regimen for Thrombolysis in Acute Myocardial Infarction

Objectives. Our aim was to design and evaluate new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic dat that improve the reperfusion success rate. Background. Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is 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 new rt-P regimen. We aimed for plateau tissue-type plasminogen activator (t-PA) plasm level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with 20-mg rt-P intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in consecutive comparative trial in 80 patients versus 2.25 106 IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-P over 90 min. Subsequently, confirmation trial of regimen 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 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 TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with 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 large-scale randomized trial is warranted.