CORONARY THROMBOLYSIS AND MYOCARDIAL SALVAGE BY TISSUE PLASMINOGEN ACTIVATOR GIVEN UP TO 4 HOURS AFTER ONSET OF MYOCARDIAL INFARCTION

doi:10.1016/S0140-6736(88)91063-X

The Lancet

Volume 331, Issue 8579, 30 January 1988, Pages 203-208

https://doi.org/10.1016/S0140-6736(88)91063-X Get rights and content

Abstract

144 patients presenting within 4 h of onset of myocardial infarction were randomised to receive either 100 mg of single-strand recombinant tissue plasminogen activator (rTPA) in 3 h (n=73) or placebo infused at the same rate (n=71). All patients were given heparin 5000 units before the infusion and heparin was continued, initially at 1000 units per hour, after the infusion. Minor bleeding was more frequent in the rTPA recipients, and during subsequent anticoagulant therapy there were three clinically significant bleeding episodes in this group. Patency of the infarct-related coronary artery was determined by coronary angiography about one week post-infarction, 125 angiograms being assessable. The infarct-related artery was patent in 70% of patients who received rTPA and in 41% of those who did not (p = 0·0015). In the 103 patients who had assessable contrast ventriculograms, the global ejection fractions were 57·7% and 51·7%, respectively (p=0·04). The difference in ventricular function was largest in patients with anterior infarction (52·7% versus 40·0%, p=0·02). The magnitude of these changes suggests an improvement in ejection fraction of 12% overall and about 30% in patients with anterior infarction.

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Since irreversible damage does not occur immediately in all cardiac muscle at risk, salvage is possible through reperfusion of the ischaemic area.23,24 Tissue plasminogen activator (TPA) given to patients up to 4 hours post-infarct appeared to provide beneficial effects through myocardial salvage, although benefit of treatment beyond this timeframe is uncertain.22,25 The earlier the TPA is administered/revascularization performed, the greater the area of myocardium that may be salvaged.
Myocardial infarction (MI) is an increasing problem, worldwide. An appreciation of its causes and morphology helps provide a basis for development of new interventions, as well as its management, and in the future prevention. Studies have shown that the myocardium does not suffer sudden and complete permanent damage, but rather that it takes time for the damage to start and to progress. It is this interval that is used to salvage myocardium, post ischaemic myocardial events, thus improving patient outcomes. This paper discusses the morphological findings at different time points and illustrates them.
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Background Data on non-Q myocardial infarctions (MI) are derived primarily from prethrombolytic era studies. Previous trials demonstrated different development rates and none reported on clinical outcomes. Methods Our goal was to determine the incidence and prognosis of non-Q-wave MI among patients with ST-segment elevation receiving thrombolysis. A retrospective analysis of 5 randomized controlled trials was made. The main outcome measures included rates of (1) transformation of ST-segment elevation to Q- and non-Q-wave MI and (2) inhospital and 1-year mortality and reinfarction among patients who subsequently develop a Q or non-Q MI postthrombolysis as compared to controls. Results Non-Q wave development was greater among patients receiving thrombolysis versus placebo/control (3.1% absolute difference, 95% CI 1.2%-5.0%). Among patients receiving thrombolysis, those who developed a non-Q MI experienced significantly lower inhospital and 1-year mortality (absolute differences −3.8% [95% CI −5.2% to −2.4%] and −6.4% [95% CI −9.9% to −3.0%], respectively) and reinfarction (absolute differences −2.9% [95% CI −4.3% to −1.6%] and −3.5% [95% CI −6.1% to −0.9%], respectively) rates, compared with those who evolved a Q MI. Inhospital and 1-year mortality was also significantly lower when compared to placebo/control patients who developed a non-Q MI (absolute differences 4.6% [95% CI −8.2% to −1.1%] and −7.5% [95% CI −12.5% to −2.5%], respectively). Conclusions Patients receiving thrombolysis more often develop a non-Q-wave MI and have a better prognosis than either those who develop a Q MI postthrombolysis or a non-Q MI after standard medical therapy. (Am Heart J 2002;144:243-50.)
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Thuspatency trials were developed, wherein patients with acute MI weregiven fibrinolytic therapy as soon as possible and then underwentangiography, where patency (defined as TIMI grade 2 or 3 flow) wasexamined. The results for both patency and recanalization trials ofstreptokinase are shown in Table 3.26, 30, 34, 37, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 Overall, the angiographic data suggest patency rates with streptokinaseof approximately 44% at 60 min and 48% at 90 min.
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¹: Participating centres are listed at the end of the article. Management CommitteeP. L. Thompson (chairman), P. Aylward, J. Federman, P. Harris, R. Hodge, N. Latt, A. Pitt, A. Thomson, A. Tonkin. Coordinating CentreDepartment of Cardiovascular Medicine, Sir Charles Gairdner Hospital, and Unit of Clinical Epidemiology, University of Western Australia. Trial coordinator: Amanda Byrne. Statistical consultants: Dallas English, Richard Parsons. Electrocardiography coding: Konrad Jamrozik. Ventriculography reading: S. Mark Nidorf.

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CORONARY THROMBOLYSIS AND MYOCARDIAL SALVAGE BY TISSUE PLASMINOGEN ACTIVATOR GIVEN UP TO 4 HOURS AFTER ONSET OF MYOCARDIAL INFARCTION

Abstract

Am J Cardiol

Lancet

Lancet

Am J Cardiol

Am J Cardiol

Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction overview of results on mortality, reinfarction and side effects from 33 randomised controlled trials

Eur Heart J

Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction

Lancet

Effect of intravenous streptokinase on left ventricular function and early survival after myocardial infarction

N Engl J Med

A prospective trial of intravenous streptokinase in acute myocardial infarction mortality, morbidity and infarct size at 21 days

N Engl J Med

Human tissue type plasminogen activator (rt.PA); from the laboratory to the bedside

Circulation

Recombinant tissue plasminogen activator (rt.PA). is it the thrombolytic agent of choice of an evolving acute myocardial Infarction?

Am J Cardiol

Coronary thrombolysis with tissue type plasminogen activator in patients with evolving myocardial infarction

N Engl J Med

The thrombolysis in myocardial infarction (TIMI) trial, phase I findings

N Engl J Med