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

Christopher P. Cannon, Carolyn H. McCabe, Daniel J. Diver, Steve Herson, Robert M. Greene, Prediman K. Shah, Raphael F. Sequeira, Ferdinand Leya, James M. Kirshenbaum, Raymond D. Magorien, Sebastian T. Palmeri, Vicki Davis, C. Michael Gibson, W. Kenneth Poole, Eugene Braunwald

Research output: Contribution to journalArticle

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Abstract

Objectives. The aim of our study was to determine a superior tbrombolytic regimen from three: anistreplase (APSAC), frontloaded 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 thrombolyticantithrombotic regimens could improve the outcome achieved with standard regimens. Methods. To address this issue, 382 patients with acute myocardial infection 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.

Original languageEnglish
Pages (from-to)1602-1610
Number of pages9
JournalJournal of the American College of Cardiology
Volume24
Issue number7
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Anistreplase
Thrombolytic Therapy
Tissue Plasminogen Activator
Myocardial Infarction
Arteries
Reperfusion

ASJC Scopus subject areas

  • Nursing(all)

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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. / Cannon, Christopher P.; McCabe, Carolyn H.; Diver, Daniel J.; Herson, Steve; Greene, Robert M.; Shah, Prediman K.; Sequeira, Raphael F.; Leya, Ferdinand; Kirshenbaum, James M.; Magorien, Raymond D.; Palmeri, Sebastian T.; Davis, Vicki; Gibson, C. Michael; Poole, W. Kenneth; Braunwald, Eugene.

In: Journal of the American College of Cardiology, Vol. 24, No. 7, 01.01.1994, p. 1602-1610.

Research output: Contribution to journalArticle

Cannon, CP, McCabe, CH, Diver, DJ, Herson, S, Greene, RM, Shah, PK, Sequeira, RF, Leya, F, Kirshenbaum, JM, Magorien, RD, Palmeri, ST, Davis, V, Gibson, CM, Poole, WK & Braunwald, E 1994, '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', Journal of the American College of Cardiology, vol. 24, no. 7, pp. 1602-1610. https://doi.org/10.1016/0735-1097(94)90163-5
Cannon, Christopher P. ; McCabe, Carolyn H. ; Diver, Daniel J. ; Herson, Steve ; Greene, Robert M. ; Shah, Prediman K. ; Sequeira, Raphael F. ; Leya, Ferdinand ; Kirshenbaum, James M. ; Magorien, Raymond D. ; Palmeri, Sebastian T. ; Davis, Vicki ; Gibson, C. Michael ; Poole, W. Kenneth ; Braunwald, Eugene. / 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. In: Journal of the American College of Cardiology. 1994 ; Vol. 24, No. 7. pp. 1602-1610.
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abstract = "Objectives. The aim of our study was to determine a superior tbrombolytic regimen from three: anistreplase (APSAC), frontloaded 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 thrombolyticantithrombotic regimens could improve the outcome achieved with standard regimens. Methods. To address this issue, 382 patients with acute myocardial infection 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.",
author = "Cannon, {Christopher P.} and McCabe, {Carolyn H.} and Diver, {Daniel J.} and Steve Herson and Greene, {Robert M.} and Shah, {Prediman K.} and Sequeira, {Raphael F.} and Ferdinand Leya and Kirshenbaum, {James M.} and Magorien, {Raymond D.} and Palmeri, {Sebastian T.} and Vicki Davis and Gibson, {C. Michael} and Poole, {W. Kenneth} and Eugene Braunwald",
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TY - JOUR

T1 - Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction

T2 - Results of the thrombolysis in myocardial infarction (TIMI) 4 trial

AU - Cannon, Christopher P.

AU - McCabe, Carolyn H.

AU - Diver, Daniel J.

AU - Herson, Steve

AU - Greene, Robert M.

AU - Shah, Prediman K.

AU - Sequeira, Raphael F.

AU - Leya, Ferdinand

AU - Kirshenbaum, James M.

AU - Magorien, Raymond D.

AU - Palmeri, Sebastian T.

AU - Davis, Vicki

AU - Gibson, C. Michael

AU - Poole, W. Kenneth

AU - Braunwald, Eugene

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Objectives. The aim of our study was to determine a superior tbrombolytic regimen from three: anistreplase (APSAC), frontloaded 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 thrombolyticantithrombotic regimens could improve the outcome achieved with standard regimens. Methods. To address this issue, 382 patients with acute myocardial infection 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.

AB - Objectives. The aim of our study was to determine a superior tbrombolytic regimen from three: anistreplase (APSAC), frontloaded 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 thrombolyticantithrombotic regimens could improve the outcome achieved with standard regimens. Methods. To address this issue, 382 patients with acute myocardial infection 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.

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