GUSTO-I

Associate Editor-In-Chief:

GUSTO-I = Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries - I Trial

Overview
The GUSTO-I trial randomized 41 021 patients with acute myocardial infarction and ST segment elevation within 6 hours of symptom onset to one of four thrombolytic strategies.

Enrollment was not restricted because of age or presentation in cardiogenic shock. Patients were excluded if they had prior stroke, active or recent bleeding, recent trauma or major surgery, non compressible vascular punctures, or previous treatment with streptokinase or anistreplase.

Treatments
Patients were randomized to receive streptokinase 1.5 million U infused for 1 hour and subcutaneous heparin 12 500 U twice daily beginning 4 hours after the commencement of streptokinase; streptokinase 1.5 million U for 1 hour and intravenous heparin, beginning with a 5000-U bolus and followed by an infusion of 1000 U adjusted to maintain an activated partial thromboplastin time (aPTT) of 60 to 85 seconds; accelerated t-PA, bolus of 15 mg and infusions of 0.75 mg/kg for 30 minutes (up to 50 mg) and 0.5 mg/kg (up to 35 mg) for the next hour, with the same intravenous heparin regimen; or combination t-PA (1 mg/kg for 1 hour, up to 90 mg, with 10% given as a bolus) and streptokinase (1 million U for 1 hour) given simultaneously through separate cannulas, with the same intravenous heparin regimen.

End Points
The primary end point was all-cause 30-day mortality. Inpatient mortality data were recorded on the main case report form. Postdischarge mortality data were collected by return postcard or by telephone follow-up. Mortality status at 30 days was known for 40 946 patients (99.8%). One-year follow-up data were available for 39 119 patients (95.3%). Secondary end points included stroke, death or stroke, and death or nonfatal, disabling stroke.

Cases of neurological deficit that were fatal or persisted for 24 hours were reviewed by a blinded, independent committee. Events were classified as primary intracranial hemorrhage, non hemorrhagic infarction, hemorrhagic conversion of infarction, and unknown.

Anatomic or diagnostic confirmation of stroke was obtained in 93% of the cases. Bleeding complications were classified as severe or life threatening if they were intracranial or resulted in hemodynamic compromise that required intervention. Moderate bleeding was defined as bleeding that required transfusion.

Statistical Methods
To describe changes in baseline characteristics and clinical outcomes with age, we arbitrarily categorized patients into four groups: <65, 65 to 74, 75 to 85, and >85 years. Discrete variables are summarized with frequencies and percentages; continuous variables are described with means ± SDs or medians and 25th and 75th percentiles. Clinical outcome variables were tabulated both by age category and by treatment assignment.

Kaplan-Meier estimates for 24-hour, 30-day, and 1-year mortality were calculated to show the treatment effects across the different age groups. These age groups were chosen to allow ready visual inspection of trends in the data.

Ordinary least-squares regression was used to determine the statistical significance of the relations between age and the other baseline characteristics. Logistic regression was used to evaluate the statistical significance of the relation between age and the 30-day outcomes of interest. Cox proportional hazard modeling techniques were used to determine the statistical significance of the relation between 1-year mortality and age. For both types of mortality models, the shapes of the relations were evaluated with cubic spline functions.