Document Detail


Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.
MedLine Citation:
PMID:  7963104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The aim of our study was to determine a superior thrombolytic regimen from three: anistreplase (APSAC), front-loaded recombinant tissue-type plasminogen activator (rt-PA) or combination thrombolytic therapy. BACKGROUND: Although thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction, it has not been clear whether more aggressive thrombolytic-antithrombotic regimens could improve the outcome achieved with standard regimens. METHODS: To address this issue, 382 patients with acute myocardial infarction were randomized to receive in a double-blind fashion (along with intravenous heparin and aspirin) APSAC, front-loaded rt-PA or a combination of both agents. The primary end point "unsatisfactory outcome" was a composite clinical end point assessed through hospital discharge. RESULTS: Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) at 60 min after the start of thrombolysis was significantly higher in rt-PA-treated patients (77.8% vs. 59.5% for APSAC-treated patients and 59.3% for combination-treated patients [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.03]). At 90 min, the incidence of both infarct-related artery patency and TIMI grade 3 flow was significantly higher in rt-PA-treated patients (60.2% had TIMI grade 3 flow vs. 42.9% and 44.8% of APSAC- and combination-treated patients, respectively [rt-PA vs. APSAC, p < 0.01; rt-PA vs. combination, p = 0.02]). The incidence of unsatisfactory outcome was 41.3% for rt-PA compared with 49% for APSAC and 53.6% for the combination (rt-PA vs. APSAC, p = 0.19; rt-PA vs. combination, p = 0.06). The mortality rate at 6 weeks was lowest in the rt-PA-treated patients (2.2% vs. 8.8% for APSAC and 7.2% for combination thrombolytic therapy [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.06]). CONCLUSIONS: Front-loaded rt-PA achieved significantly higher rates of early reperfusion and was associated with trends toward better overall clinical benefit and survival than those achieved with a standard thrombolytic agent or combination thrombolytic therapy. These findings support the concept that more rapid reperfusion of the infarct-related artery is associated with improved clinical outcome.
Authors:
C P Cannon; C H McCabe; D J Diver; S Herson; R M Greene; P K Shah; R F Sequeira; F Leya; J M Kirshenbaum; R D Magorien
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  24     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1994-12-16     Completed Date:  1994-12-16     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1602-10     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
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MeSH Terms
Descriptor/Qualifier:
Aged
Anistreplase / adverse effects,  therapeutic use*
Aspirin / therapeutic use
Double-Blind Method
Drug Therapy, Combination
Female
Follow-Up Studies
Heparin / therapeutic use
Humans
Infusions, Intravenous
Male
Middle Aged
Myocardial Infarction / drug therapy*,  mortality
Thrombolytic Therapy*
Tissue Plasminogen Activator / therapeutic use*
Vascular Patency
Chemical
Reg. No./Substance:
50-78-2/Aspirin; 81669-57-0/Anistreplase; 9005-49-6/Heparin; EC 3.4.21.68/Tissue Plasminogen Activator

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