Benefit of Early Sustained Reperfusion in Patients With Prior Myocardial Infarction (The GUSTO-I Trial) David B. Brieger, MBBS, PhD, Koon-Hou Mak, MBBS, Harvey D. White, MBChB, DSc, Neal S. Kleiman, MD, David P. Miller, MS, Alec Vahanian, MD, Allan M. Ross, MD, Robert M. Califf, MD, and Eric J. Topol, MD for the GUSTO-I Investigators The primary objective of this study was to characterize a large cohort of patients receiving thrombolytic ther- apy for acute myocardial infarction with respect to the group with a prior event. Patients were randomly assigned to 1 of 4 thrombolytic strategies. Baseline characteristics, 30-day outcomes, and 1-year mortal- ity were compared between patients with (n  6,704) and without (n  34,143) prior myocardial infarction. Patients with prior myocardial infarction presented to the hospital earlier than those having their first event, but institution of thrombolytic therapy was delayed. Mortality at 30 days (11.7% vs 5.9%, p  0.001) and 1 year (17.3% vs 8.2%, p <0.001) was greater among patients with prior infarction, and indepen- dent of other demographic variables. Accelerated al- teplase was more effective than streptokinase or com- bination therapy (30-day mortality 10.4% vs 12.2%, p  0.012; 1-year mortality 15.9% vs 17.8%, p  0.041). Infarct vessel patency did not differ between those with and without prior myocardial infarction (67.3% vs 67% at 90 minutes, p  0.92); however, recurrent ischemia was more common in patients with prior myocardial infarction. Patients with healed myo- cardial infarction should be educated to ensure early hospital admission if they develop symptoms sugges- tive of acute infarction, and upon hospital arrival should be promptly triaged to receive reperfusion therapy with accelerated alteplase. 1998 by Ex- cerpta Medica, Inc. (Am J Cardiol 1998;81:282–287) I n the Gruppo Italiano per lo Studio della Streptochi- nasi nell’Infarto miocardico (GISSI) study, patients with previous myocardial infarction appeared not to benefit from thrombolysis. 1 In the International Study of Infarct Survival (ISIS-2), streptokinase reduced the incidence of vascular death relative to placebo in this subgroup, 2 and the Fibrinolytic Therapy Trialists’ Collaborative Group 3 reported that patients with prior myocardial infarction experienced a mortality reduc- tion from thrombolytic therapy. 3 Management of these patients in the thrombolytic era would be aided by a clearer characterization of their response to thrombo- lytic therapy. We have therefore performed a post-hoc analysis of the Global Utilization of Streptokinase and TPA for occluded arteries (GUSTO)-I trial, compar- ing the subgroup of patients who have a history of myocardial infarction and receive thrombolysis with those without this history. This has enabled us to critically analyze their clinical and angiographic re- sponse to thrombolytic therapy. METHODS Patient population: The GUSTO-I trial included a total of 41,021 patients, presenting within 6 hours of the onset of symptoms that were consistent with myocardial infarction and ST elevation between December 1990 and February 1993. Data on whether the patients had previously experienced a myocardial infarction based on history and/or pre- senting electrocardiogram were collected by the enrolling physician and entered on the case report form. The specifics of the design of the study, patient inclusion and exclusion criteria, data collec- tion and management, and quality assurance have been previously described. 4 Randomization and treatment strategies: Patients were randomly assigned to: (1) streptokinase 1.5 million U over 60 minutes with subcutaneous hep- arin 12,500 U twice daily beginning 4 hours after the start of thrombolytic therapy, (2) streptokinase 1.5 million U over 60 minutes with intravenous heparin as a bolus of 5,000 U and then 1,000 U/hour, with dose adjustment to maintain an acti- vated partial thromboplastin time of 60 to 85 sec- onds; (3) accelerated alteplase bolus of 15 mg and then infusion of 0.75 mg/kg (up to 50 mg) over 30 minutes and 0.5 mg/kg (up to 35 mg) over the next 60 minutes accompanied by the same intravenous heparin regimen; (4) a combination of intravenous alteplase (1.0 mg/kg over 60 minutes, not to exceed 90 mg, with 10% given as a bolus) and streptoki- nase (1.0 million U over 60 minutes) given concur- rently but through separate catheters, accompanied by the same intravenous heparin regimen. 4 From the Department of Cardiology and the Joseph J. Jacobs Center for Vascular Biology, The Cleveland Clinic Foundation, Cleveland, Ohio; the Department of Medicine, Duke University Medical Center, Durham, North Carolina; the Division of Cardiology, George Wash- ington University, Washington, DC; the Section of Cardiology, De- partment of Medicine, Baylor College of Medicine, Houston, Texas; the Cardiology Department, Green Lane Hospital, Auckland, New Zealand; and the Cardiology Service, Hopital Tenon, Paris, France. Manuscript received June 12, 1997; revised manuscript received and accepted November 4, 1997. Address for reprints: Eric J. Topol, MD, The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk F-25, Cleveland, Ohio 44195. 282 ©1998 by Excerpta Medica, Inc. 0002-9149/98/$19.00 All rights reserved. PII S0002-9149(97)00909-0