RSS Feeds
Large-Scale Trials of Thrombolytic Therapy for Acute Myocardial Infarction: GISSI-2, ISIS-3, and GUSTO-1
- Paul M. Ridker, MD;
- Christopher O'Donnell, MD;
- Victor J. Marder, MD; and
- Charles H. Hennekens, MD
- Brigham and Women's Hospital, Boston, MA 02215-1204. University of Rochester, Rochester, NY 14642. Harvard Medical School, Boston, MA 02215. Requests for Reprints: Paul M. Ridker, MD, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215-1204.
With the release of the GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator to Treat Occluded Arteries [1]) study results, data are now available from three large-scale randomized trials that directly compared the thrombolytic agents most commonly used in the United States (Table 1). When examined both individually and together, these three trials show, at most, small absolute differences among agents, in terms of both lives saved and major complications (including hemorrhagic stroke). All three trials also indicate that the choice of thrombolytic agent is less important for patient survival than the delay time to initiation of treatment. This time period often includes long in-hospital delays owing to inadequate emergency room staffing and inadequate training in the appropriate administration of thrombolytic therapy.
- In this window
- In a new window
We review GISSI-2 (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico [2, 3]), ISIS-3 (Third International Study of Infarct Survival [4]), and GUSTO-1 [1] to provide a rational basis for health providers to determine optimal patient care and resource allocation.
Currently, three thrombolytic regimens are approved by the Food and Drug Administration (FDA) for use in patients with acute myocardial infarction; two of these regimens were directly compared in GISSI-2, and all were directly compared in ISIS-3.
In GISSI-2 and its International Study Group extension, 20 891 patients with acute myocardial infarction who were admitted to coronary care units within 6 hours of symptom onset were enrolled in a randomized trial comparing the benefits and risks of streptokinase (1.5 million U over 30 to 60 minutes) and tissue plasminogen activator (tPA) (alteplase, 100 mg over 3 hours). All patients were given aspirin (325 mg) daily for 30 days and were also randomly assigned to receive either heparin (12 500 IU subcutaneously twice daily starting within 12 hours of thrombolysis) or no heparin.
Overall, no significant differences …
