Copyright © 1996 by the European Society of Cardiology.
© 1996 The European Society of Cardiology
Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency
The GUSTO Enzyme Substudy
Thoraxcenter, Erasmus University Rotterdarn Enschede, The Netherlands
*Cardiovascular Research Institute Maastricht Maastricht, The Netherlands
Medisch Spectrum Twente Enschede, The Netherlands
Centre Hospitalier Universitaire Caen, France
University Clinics Basel, Switzerland
Received 7 July 1995; accepted 7 August 1995.
Correspondence: Maarten L. Simoons, MD, Thoraxcenter, BD 434, Erasmus University/Dijkzigt Hospital, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Abstract
BACKGROUND: The recent international GUSTO trial of 41 021 patients with acute myocardial infarction demonstrated improved 90-mm infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients.
METHODS: A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (iv.) heparin, tissue plasminogen activator with iv. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 mm after treatment.
RESULTS: Infarct size was 3·72 g-eq . 1–1 in patients with adequate coronary perfusion (TIMI-3) at the 90 mm angi-ogram and larger in patients with TIMI-2 (4·35 g-eq . 1–1) or TIMI 0–1 (5·07 g-eq . 1–1)flow (P=0·024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2+3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram- equivalents (g-eq) of myocardium, was 4·4, 4·5, 3·9 and 3·9 g-eq per litre of plasma (P=0·04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5·3, 6·6, 14·0 and 13·6% of total HBDH release was complete (P<0·000l for streptokinase vs tissue plasminogen activator).
CONCLUSIONS: Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.
Key Words: Thrombolysis • infarct size • enzymes • GUSTO
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