Correspondence
Thrombolytic Therapy for Myocardial Infarction
N Engl J Med 1994; 330:1089-1090April 14, 1994
- Article
To the Editor:
The GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) angiographic investigators (Nov. 25 issue)1 concluded that normal coronary flow in the infarct-related artery early after myocardial infarction is associated with a sustained improvement in the ejection fraction, as compared with reduced flow or an absence of flow. They further demonstrated that accelerated treatment with recombinant tissue plasminogen activator (t-PA) resulted in early normal flow (at 90 minutes) more frequently than treatment with streptokinase and heparin or combination treatment with t-PA and streptokinase.
One might have expected that any degree of improvement in early patency would lead to an improvement in left ventricular function, but the beneficial effects of improved flow on left ventricular function, as assessed by several measurements, including ejection fraction and wall motion, are noteworthy only when restoration of flow is complete (grade 3 flow, as defined in the Thrombolysis in Myocardial Infarction [TIMI] trial2). With the exception of wall motion, no measure of left ventricular function was better in the patients with TIMI grade 2 flow at 90 minutes and at five to seven days than in the patients with grade 1 flow or grade 0 flow. One might also have expected that when left ventricular function was examined according to treatment group, the group given accelerated t-PA would have better left ventricular function because of the increased rate of early complete restoration of flow. In fact, there was no overall difference in ejection fraction among the treatment groups at 90 minutes. Other measures of left ventricular function were little better, a fact somewhat obscured by selective comparison of the groups. Furthermore, many benefits for left ventricular function that were suggested early on were lost at five to seven days.
Early complete patency may well benefit left ventricular function, but this trial has not convincingly shown that a regimen of accelerated t-PA is any better than streptokinase combined with intravenous heparin, the current standard regimen in the United Kingdom.
2 ReferencesH. Montgomery, B.Sc., M.R.C.P.
M.E. Speechly-Dick, B.Sc., M.R.C.P.
University College London Medical School, London WC1E 6DB, United Kingdom1
The GUSTO Angiographic Investigators
Full Text | Web of Science | Medline2
Chesebro JH ,Knatterud G ,Roberts R , et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: clinical findings through hospital discharge. Circulation 1987;76:142-154
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To the Editor:
Recently, studies of thrombolysis in myocardial infarction have focused on differences in outcome between groups receiving various thrombolytic agents. The members of the GUSTO trial1 were the first to test an alternative dosing regimen, in which recombinant t-PA was given at an accelerated rate. This was associated with a remarkably high rate of early patency of the infarct-related vessel and low mortality during the first 30 days.
It is surprising that this new regimen was not compared with a conventional dosing regimen. Furthermore, streptokinase was administered according to the traditional scheme2. To our knowledge, an alternative dosing regimen of streptokinase has never been evaluated in a sufficiently large randomized trial.
In view of the 10-fold higher cost of t-PA as compared with streptokinase, we wonder whether an accelerated infusion of streptokinase would prove more effective than the conventional infusion and perhaps achieve comparable results in terms of early patency in the infarct-related vessel and low 30-day mortality.
2 ReferencesChristoph Pechlaner, M.D.
Peter Lechleitner, M.D.
Innsbruck University, A-6020 Innsbruck, Austria1
The GUSTO Investigators
Full Text | Web of Science | Medline2
ISIS-3 (Third International Study of Infarct Survival) Collaborative Group
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Author/Editor Response
Dr. Ross, chairman of the GUSTO Angiographic Substudy, replies:
To the Editor: We agree with Montgomery and Speechly-Dick that early after treatment, the advantages in the t-PA group lay in regional (infarct zone) function rather than the global ejection fraction. Because of compensatory hyperkinesis outside the infarct zone, such a result was expected (hence, the emphasis on numerous measures of regional function). Although the differences favoring t-PA treatment are not large, they are clearly statistically significant (and clinically important). As Table 4 of our article indicates, at five to seven days all treatment groups had small improvements in all measures of regional wall motion; however, rank-order analysis will demonstrate that the t-PA group continued to have the greatest advantage. After comparing t-PA with streptokinase, the GUSTO investigators concluded that there was an incremental advantage in the preservation of ventricular function compatible with the magnitude of superiority in early patency and with the observed difference in mortality rates.
With respect to dosing regimens, we refer Drs. Pechlaner and Lechleitner to previous trials1,2 that establish the clinical efficacy and quicker reperfusion ability of the accelerated-t-PA regimen used in the GUSTO trial (as compared with conventional three-hour infusion). With respect to streptokinase dosing regimens, a recent study by Taylor et al.3 compared conventional t-PA administration with accelerated streptokinase administration and found superior left ventricular function in patients with myocardial infarctions who received the t-PA.
3 ReferencesAllan M. Ross, M.D.
George Washington University, Washington, DC 20037for the GUSTO Angiographic Investigators
1
Neuhaus KL ,Feuerer W ,Jeep-Tebbe S ,Niederer W ,Vogt A ,Tebbe U . Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator. J Am Coll Cardiol 1989;14:1566-1569
CrossRef | Web of Science | Medline2
Carney RJ ,Murphy GA ,Brandt TR , et al. Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. J Am Coll Cardiol 1992;20:17-23
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Taylor GJ ,Moses HW ,Koester D , et al. A difference between front-loaded streptokinase and standard-dose recombinant tissue-type plasminogen activator in preserving left ventricular function after acute myocardial infarction. Am J Cardiol 1993;72:1010-1014
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