Author + information
- Received April 28, 1997
- Revision received July 29, 1997
- Accepted August 21, 1997
- Published online December 1, 1997.
- Dietrich C Gulba, MDAB,* (, )
- Paul Tanswell, PhDC,
- Ralf Dechend, MDA,
- Markus Sosada, MDB,
- Angelika Weis, MDA,
- Jürgen Waigand, MDA,
- Frank Uhlich, MDA,
- Sven Hauck, MDA,
- Stefan Jost, MDB,
- Wolf Rafflenbeul, MD, FACCB,
- Paul R Lichtlen, MD, FACCB and
- Rainer Dietz, MDA
- ↵*Dr. Dietrich C. Gulba, Humbold University of Berlin, Franz-Volhard Hospital, Wiltbergstrasse 50, D-13125 Berlin, Germany.
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 106IU 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.
- Received April 28, 1997.
- Revision received July 29, 1997.
- Accepted August 21, 1997.
- The American College of Cardiology