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Thrombolytic therapy: pre- and post-GISSI-2, ISIS-3, and GUSTO-1
1Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215.
Insights
Thrombolytic therapy choice is less critical than timely treatment for acute myocardial infarction. Early treatment improves survival, and all agents are effective up to 12 hours post-symptom onset.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Large-scale randomized trials (GISSI-2, ISIS-3, GUSTO-1) evaluated thrombolytic regimens for acute myocardial infarction.
- Over 100,000 patients were included in these global trials.
Purpose of the Study:
- To compare the efficacy and safety of different thrombolytic agents.
- To assess the impact of treatment timing on patient outcomes.
Main Methods:
- Analysis of data from three major randomized trials comparing thrombolytic therapies.
- Examination of mortality, major complications (including hemorrhagic stroke), and treatment delay.
Main Results:
- Small absolute differences in lives saved and complications between thrombolytic agents.
- Tissue plasminogen activator (TPA) associated with increased strokes and cerebral bleeds; incremental mortality benefit unclear.
- Treatment delay is more critical for survival than agent choice.
- Differences in efficacy/safety are minimal for patients presenting >4 hours post-symptom onset.
- All agents effective up to 12 hours post-symptom onset.
- Patients excluded due to age, gender, ECG findings, or late arrival benefit from thrombolysis if no contraindications exist.
- Lower thrombolytic therapy utilization in the US compared to European countries.
Conclusions:
- Clinical strategy should prioritize increasing thrombolytic utilization for all eligible patients, especially late arrivers.
- Timely initiation of thrombolytic therapy is paramount for acute myocardial infarction survival.
- Despite minor differences, thrombolytic agents are broadly effective, emphasizing prompt treatment over agent selection.
Abstract:
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)