Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction

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Item Type:	Article
Title:	Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction
Creators Name:	Gulba, D.C., Tanswell, P., Dechend, R., Sosada, M., Weis, A., Waigand, J., Uhlich, F., Hauck, S., Jost, S., Rafflenbeul, W., Lichtlen, P.R. and Dietz, R.
Abstract:	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.
Keywords:	Blood Coagulation Tests, Coronary Angiography, Drug Administration Schedule, Intravenous Infusions, Intravenous Injections, Myocardial Infarction, Plasminogen Activators, Prospective Studies, Streptokinase, Thrombolytic Therapy, Time Factors, Tissue Plasminogen Activator, Vascular Patency
Source:	Journal of the American College of Cardiology
ISSN:	0735-1097
Publisher:	Elsevier
Volume:	30
Number:	7
Page Range:	1611-1617
Date:	December 1997
Official Publication:	https://doi.org/10.1016/S0735-1097(97)00370-7
PubMed:	View item in PubMed

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