Clinical Trials with Alteplase (RT-pa) in Acute Myocardial Infarction
Alteplase (recombinant human tissue plasminogen activator, rt-PA) first became available for clinical trials in acute myocardial infarction in 1984 (1). At this time there was already considerable experience with thrombolysis using intracoronary streptokinase (2), and a consensus that the benefits of coronary thrombolysis operated through the early restoration of coronary patency. The potential benefits of rt-PA compared with streptokinase as seen in 1984 are listed in table 1 —the principal hope being that a “thrombus specific” agent such as rt-PA would provide more effective and rapid thrombolysis with a minimum of bleeding complications. The endpoint in the earliest trials (TIMI 1 and ECSG 1) was angiographic coronary patency — the “hardest” endpoint realistically attainable with the limited amounts of rt-PA then available. The results of these studies were favourable to rt-PA in comparison both with placebo (ECSG-1) and streptokinase (ECSG-2 and TIMI-1) but it was clear that larger studies would be needed both to provide adequate safety data for registration, and to provide more clearcut evidence concerning “outcome” measurements such as mortality and left ventricular function. Moreover the TIMI-1 study had raised a worry concerning the apparent high rate of reocclusion following rt-PA thrombolysis (3,4). The question of reocclusion was specifically addressed in ECSG-3, with reassuring results. Nevertheless, concern about reocclusion undoubtedly influenced subsequent trials both in terms of the use of a prolonged rt-PA infusion and a feeling that results might be further improved by combining thrombolysis with early angioplasty.
KeywordsAcute Myocardial Infarction Intravenous Streptokinase Intracoronary Streptokinase Coronary Thrombolysis Intravenous Tissue Plasminogen Activator
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- 3.The TIMI study group. The thrombolysis in myocardial infarction (TIMI) trial. Phase 1 findings. N. Engl. J. Med., 312:932–36 (1985).Google Scholar
- 5.Gruppo Italiano per lo Studi deela Streptochinasi nell’ Infarto miocardico (GISSI). Effectiveness of intravenous thromboytic therapy in acute myocardial infarction. Lancet, i:397–401 (1986).Google Scholar
- 9.M. L. Simoons, A. E. R. Arnold, A. Betriu et al. Thrombolysis with rt-PA in acute myocardial infarction: no additional benefit of immediate PTCA. Lancet, i;(1988).Google Scholar
- 10.F. van de Werf, A. E. R. Arnold, and the European Cooperative Study Group for Recombinant Tissue Plasminogen Activator. Effect of intravenous tissue plasminogen activator on infarct size, left ventricular function and survival in patients with acute myocardial infarction. Br. Med. J., (1988).Google Scholar
- 12.E. Passamani. Thrombolysis in myocardial infarction: the NHLBI experience, in: Sobel B.E., Collen D., Grossbard EB (eds). Tissue Plasminogen Activator in Thrombolytic Therapy. M. Dekker, New York/Basel, pp75–86 (1986).Google Scholar
- 16.M. O’Rourke, D. Baron, A. Keogh et al. Limitation of myocardial infarction by early infusion of recombinant tissue type plasminogen activator. Circulation,77(6):13311–5 (1988).Google Scholar
- 17.National Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet, i:203–8 (1988).Google Scholar
- 19.ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected myocardial infarction: ISIS-2. Lancet, ii:349–60 (1988).Google Scholar