Thrombolytic therapy: pre- and post-GISSI-2, ISIS-3, and GUSTO-1.
At present, data are available from three large-scale randomized trials of mortality that directly compared different thrombolytic regimens, namely, GISSI-2, ISIS-3, and GUSTO-1. These trials randomized over 100,000 patients worldwide. When examined individually as well as in aggregate, these trials demonstrate at most only small absolute differences between thrombolytic agents both in terms of lives saved and major complications, including hemorrhagic stroke. Specifically, TPA produces more strokes and cerebral bleeds, but whether or not there is a small incremental mortality benefit is not yet clear. All three trials indicate that the choice of thrombolytic agent is much less important to ultimate survival than is the delay time between onset of symptoms and initiation of treatment. Further, any potential differences in efficacy and safety between the available thrombolytic agents are unlikely to pertain to the majority of infarct patients who present to hospitals more than 4 h after the onset of symptoms. Since all three agents appear to be effective when given up to 12 h after the onset of symptoms, a clinical strategy must be adopted to increase thrombolytic utilization for late arrivers regardless of which agent is chosen. Patients excluded from thrombolytic therapy because of age, gender, presence of bundle-branch block on admitting electrocardiogram, and late arrival in the emergency department in fact benefit substantially from thrombolysis as long as contraindications to the drug do not exist. Nonetheless, only one-third of U.S. patients with acute myocardial infarction receive thrombolytic therapy, compared with over two-thirds of patients in the United Kingdom and several other European countries.(ABSTRACT TRUNCATED AT 250 WORDS)
Hennekens
C H
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Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215.
D016255:Anistreplase / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D016255:Anistreplase; D006493:Heparin; D013300:Streptokinase; D010959:Tissue Plasminogen Activator