Author + information
- Charles H. Hennekens, MD, DrPH, FACC∗∗,‡,§,1,
- Christopher J. O'Donnell, MD∗,†,
- Paul M. Ridker, MD, FACC∗ and
- Victor J. Marder, MD‖,2
- ↵∗Address for correspondence: Dr. Charles H. Hennekens, 900 Commonwealth Avenue East, Boston, Massachusetts 02215.
Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS-3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States—tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)—all reduce mortality when given to patients with acute evolving myocardial infarction. Further, it is clear that thrombolytic therapy given to such patients presenting up to 12 h after onset of symptoms reduces the mortality rate by ∼20%, that aspirin therapy for patients presenting up to 24 h reduces the mortality rate by ∼23% and that the benefits of thrombolytic therapy and aspirin are additive. Finally, and of most importance, the earlier administration as well as the more widespread use of thrombolytic therapy and aspirin would save many more lives. The totality of evidence clearly indicates that streptokinase produces significantly fewer strokes and cerebral hemorrhages than either t-PA or APSAC. Whether or not accelerated t-PA has a small advantage for mortality is less conclusive. At present, any small differences in safety, efficacy and ease of administration of different thrombolytic agents are far outweighed by the large benefits that would accrue from earlier administration and wider utilization of any of these drugs.