60-MINUTE ALTEPLASE PROTOCOL - A NEW ACCELERATED RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR REGIMEN FOR THROMBOLYSIS IN ACUTE MYOCARDIAL-INFARCTION

Objectives. Our aim was to design and evaluate a new and easily admini stered recombinant tissue type plasminogen activator (rt-PA) regimen f or thrombolysis in acute myocardial infarction (AMI) based on establis hed pharmacokinetic data that improve the reperfusion success rate. Ba ckground. Rapid restoration of Thrombolysis in Myocardial Infarction ( TIMI) grade 3 flow is a primary predictor of mortality after thromboly sis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolys is of only 50% to 60% indicate an obvious need for improved thrombolyt ic regimens. Methods. Pharmacokinetic simulations were performed to de sign a new rt-PA regimen. We aimed for a plateau tissue-type plasminog en 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 in travenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative tria l 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 confirm ation trial of regimen A in 254 consecutive patients was performed wit h angiographic assessment by independent investigators of patency at 9 0 min. Results. The comparative phase of the trial yielded, respective ly, 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). I n the confirmation phase of the trial, regimen A yielded 81.1% TIMI gr ade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 16 9 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir l evels of fibrinogen, plasminogen and alpha(2)-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fif ty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood tr ansfusions. Conclusions. The 60-min alteplase thrombolysis in AMI prot ocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no i ndication 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 com parison with established thrombolytic regimens in a large-scale random ized trial is warranted. (C) 1997 by the American College of Cardiolog y.