La Diffe´rence

HomeCirculationVol. 94, No. 6La Diffe´rence Free AccessResearch ArticleDownload EPUBAboutView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticleDownload EPUBLa Diffe´renceLong-term Benefit of One Thrombolytic Over Another Robert Roberts Robert RobertsRobert Roberts the Bugher Foundation for Molecular Biology, Baylor College of Medicine, Houston, Tex. Search for more papers by this author Originally published15 Sep 1996https://doi.org/10.1161/01.CIR.94.6.1203Circulation. 1996;94:1203–1205Recanalization of coronary arteries, induced by either thrombolytic therapy or angioplasty, has revolutionized the management of acute myocardial infarction. The mean in-hospital death rate for patients who reach the hospital in time and receive thrombolytic therapy is ≈6% to 7%.1 This is a dramatic reduction compared with the death rate in the 1960s of 30% to 35%. Thrombolytic therapy is easy to administer and is carried out routinely in community hospitals throughout North America and many other parts of the world. In addition to the reduced death rate, there is likely to be a reduced morbidity; however, this is more difficult to prove. Clinical trials to date on thrombolytics have concentrated on mortality, in part because this is the major, if not the sole, end point required by the Food and Drug Administration to approve a new drug.In the original Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries (GUSTO-I) trial,1 the 41 021 patients who were enrolled received one of four thrombolytic agents. Patients who had ST-segment elevation and presented within 6 hours of onset were enrolled unless there was a contraindication. Enrollment had no age limit and included patients in cardiogenic shock and those with previous bypass surgery; thus, this population was highly representative of the patient population at large presenting with acute myocardial infarction.The overall objective of GUSTO-I was to compare four thrombolytic regimens: streptokinase followed by subcutaneous heparin, streptokinase followed by intravenous heparin, tissue plasminogen activator (TPA*) ≤100 mg given over 60 minutes followed by intravenous heparin, and a combination of intravenous TPA and streptokinase followed by intravenous heparin. All patients received aspirin and atenolol if there were no contraindications. The 30-day mortality rate in that trial was 6.3% for patients who received accelerated TPA, 7.2% for those receiving streptokinase and subcutaneous heparin, 7.4% for those on streptokinase and intravenous heparin, and 7% for those receiving the combination therapy. Thus, the overall benefit of TPA over streptokinase was an absolute 1% reduction in mortality and ≈14% reduction in relative risk.The study reported in this issue2 provides the results of a 1-year follow-up on the GUSTO-I patients and shows that the benefit of TPA over that of streptokinase observed at 30 days of a 1% reduction in mortality was sustained (9.1% for TPA versus 10.1% for streptokinase, P2000 patients, serial angiography was performed in the acute phase, and TPA was shown to open more vessels than streptokinase (81% verses 56%) at 90 minutes; thus, one may anticipate that at discharge patients receiving TPA would have more open vessels than those who received streptokinase. It is predicted but not proved that an open vessel would offer protection against subsequent clinical events, which could lead to less mortality at the end of 1 year than in the streptokinase group. However, coronary angiography performed in this same subset at 180 minutes showed that the patency in patients receiving TPA was now essentially the same as that in patients receiving streptokinase (76% and 73%, respectively). Similarly, at 24 hours, the patencies were virtually identical. Thus, in the GUSTO-I trial, a difference in vessel patency does not appear to be an indication for further improvement in the TPA group over that in the streptokinase groups. These findings are also relevant to future studies testing the hypothesis that an open vessel at discharge is better than a closed vessel. Studies testing this hypothesis should perhaps recognize that baseline patency for such a trial is best determined at least 24 hours after thrombolytic therapy, and perhaps that percentage of patients who have sustained occlusion should be targeted for enrollment.In summary, optimism should prevail in view of the findings by Califf et al2 in the follow-up of 41 021 patients after thrombolytic therapy. It is to be commended that therapy today for acute myocardial infarction can reduce the acute mortality to 6% or 7% and that the subsequent mortality over the next year is only 3%. It is also suggested that a further reduction in acute mortality (2% to 4%) would be expected to be sustained. The cardiologist needs to be reminded that despite a 6% to 7% in-hospital mortality rate for acute myocardial infarction in patients receiving thrombolytic therapy, there are still 300 000 to 400 000 patients who die of acute myocardial infarction before reaching the hospital. There is every reason to believe that prehospital thrombolytic therapy would translate into significant salvage. Only after we have conquered prehospital thrombolysis can we reap the full benefit of this therapeutic revolution for the treatment of acute myocardial infarction.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.*AHA uses the acronym TPA because t-PA is a trademarked name.FootnotesCorrespondence to Robert Roberts, MD, Section of Cardiology, Baylor College of Medicine, 6550 Fannin, MS SM677, Houston TX 77030. References 1 GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med.1993; 329:673-682.CrossrefMedlineGoogle Scholar2 Califf RM, White HD, Van de Werf F, Sadowski Z, Armstrong PW, Vahanian A, Simoons ML, Simes RJ, Lee KL, Topol EJ, for the GUSTO-I Investigators. One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. Circulation.1996; 94:1233-1238.CrossrefMedlineGoogle Scholar3 Lee KL, Califf RM, Simes J, Van de Werf F, Topol EJ, for the GUSTO Investigators. Holding GUSTO up to the light. Ann Intern Med.1994; 120:876-881.CrossrefMedlineGoogle Scholar4 Ridker PM, O'Donnel CJ, Marde VJ, Hennekens CH. A response to ‘Holding GUSTO up to the light.' Ann Intern Med.1994; 120:882-885.CrossrefGoogle Scholar5 GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med.1993; 329:1615-1622.CrossrefMedlineGoogle Scholar6 Farkouh ME, Lang JD, Sackett DL. Thrombolytic agents: the science of the art of choosing the better treatment. Ann Intern Med.1994; 120:886-888.CrossrefMedlineGoogle Scholar7 Huth EJ. ‘In the balance': weighing the evidence. Ann Intern Med.1994; 120:889.CrossrefMedlineGoogle Scholar8 Wilcox RG, Von der Lipp G, Olsson CG, Jensen G, Skene AM, Hampton JR. Effects of alteplase in acute myocardial infarction: 6-month results from the ASSET study−Anglo-Scandinavian Study of Early Thrombolysis. Lancet.1990; 335:1175-1178.MedlineGoogle Scholar9 AIMS Trial Study Group. Long-term effects of intravenous anistreplase in acute myocardial infarction. Lancet.1990; 335:427-431.CrossrefMedlineGoogle Scholar10 Simoons ML, Vos J, Tijssen JG, Vermeer F, Verheugt FW, Krauss XH, Cats VM. Long-term benefit of early thrombolytic therapy in patients wtih acute myocardial infarction: 5-year follow-up of a trial conducted by the Interuniversity Cardiology Institute of the Netherlands. J Am Coll Cardiol.1989; 14:1609-1615.CrossrefMedlineGoogle Scholar11 Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico. Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Lancet.1987; 2:871-874.MedlineGoogle Scholar12 Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico. Six-month survival in 20,891 patients with acute myocardial infarction randomised between alteplase and streptokinase with or without heparin: GISSI-2 and International Study Group. Eur Heart J.1992; 13:1692-1697.CrossrefMedlineGoogle Scholar13 Baigent C, Collins R, for the ISIS Collaborative Group. ISIS-2: 4-year mortality follow-up of 17,187 patients after fibrinolytic and antiplatelet therapy in suspected acute myocardial infarction. Circulation. 1993;88(suppl I):I-291. Abstract.Google Scholar14 Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O'Keefe J, Overlie P, Donohue B, Chelliah N, Timmis GC, Vliestra RE, Strzelecki M, Puchrowicz-Ochocki S, O'Neill WW, for the Primary Angioplasty in Myocardial Infarction Study Group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction: the Primary Angioplasty in Myocardial Infarction Study. N Engl J Med.1993; 328:673-679.CrossrefMedlineGoogle Scholar15 Van de Werf F. Thrombolysis for acute myocardial infarction: why is there no extra benefit after hospital discharge? Circulation.1995; 91:2862-2864.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Goldschmidt P, Lopes N, Crawford L and Becker R (2007) Atherothrombosis and Coronary Artery Disease Platelets, 10.1016/B978-012369367-9/50797-7, (629-655), . Coccolini S, Berti G and Maresta A (1998) The magnitude of the benefit from preCCU thrombolysis in acute myocardial infarction: a long term follow up, International Journal of Cardiology, 10.1016/S0167-5273(98)00063-1, 65, (S49-S56), Online publication date: 1-May-1998. September 15, 1996Vol 94, Issue 6 Advertisement Article InformationMetrics Copyright © 1996 by American Heart Associationhttps://doi.org/10.1161/01.CIR.94.6.1203 Originally publishedSeptember 15, 1996 KeywordsthrombosisthrombolysisEditorialsprognosismyocardial infarction Advertisement