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Overview: rationale of thrombolysis in treating acute myocardial infarction
1Department of Medicine, University of California, School of Medicine, San Francisco.
Insights
Thrombolytic agents significantly reduce early mortality in acute myocardial infarction when given within 6 hours. Further research is ongoing to determine their role in other acute ischemic syndromes.
Area of Science:
- Cardiology
- Thrombosis Research
Background:
- Thrombolytic therapy for coronary thrombosis emerged in the 1950s.
- Early trials with streptokinase were inconclusive, but later studies confirmed its efficacy.
- Key findings in 1976 and 1980 highlighted prompt recanalization and high rates of coronary artery occlusion in myocardial infarction.
Purpose of the Study:
- To review the historical development and current status of thrombolytic therapy for acute myocardial infarction.
- To evaluate the impact of thrombolytic agents on mortality rates.
- To investigate the potential role of thrombolysis in non-transmural myocardial infarction and other acute ischemic syndromes.
Main Methods:
- Historical review of clinical trials and observational studies.
- Analysis of mortality data from thrombolytic treatment trials.
- Ongoing studies like TIMI-3B investigating thrombolysis in non-Q-wave myocardial infarction and unstable angina.
Main Results:
- Thrombolytic agents like recombinant tissue plasminogen activator and streptokinase markedly reduce early mortality in acute myocardial infarction when administered within 6 hours.
- Significant coronary artery occlusion is common in the early hours of infarction.
- Benefits are not yet established for myocardial infarction with ST-segment depression.
Conclusions:
- Thrombolytic therapy is a proven intervention for reducing early mortality in acute myocardial infarction.
- Further research is needed to define the role of thrombolysis in acute ischemic syndromes beyond transmural myocardial infarction.
Abstract:
Treatment of coronary thrombosis with thrombolytic agents was first introduced in the 1950s. Clinical trials, primarily with streptokinase during the 1960s and 1970s, addressed the effects of thrombolysis on mortality rates after acute myocardial infarction, but were inconclusive and largely ignored. In 1976, Chazov et al. from the Soviet Union demonstrated that intracoronary streptokinase could produce prompt recanalization of a totally occluded infarct-related artery. In 1980, DeWood et al. demonstrated that 87% of patients with classic Q-wave myocardial infarction had total occlusion from coronary thrombosis of the infarct-related artery when studied during the first 4 hours of their infarction and that 65% of these arteries were still occluded when patients were studied between 12 and 24 hours after infarction. These observations stimulated renewed interest in thrombolytic therapy for acute myocardial infarction. Mortality trials have subsequently demonstrated that agents such as recombinant tissue plasminogen activator, streptokinase, and anisoylated plasminogen streptokinase activator complex remarkably reduce early mortality rates among patients with acute myocardial infarction when treatment is instituted within the first 6 hours of infarction. Benefit has yet to be demonstrated, however, in patients with acute myocardial infarction characterized by ST-segment depression. This whole area is currently under study by the TIMI investigators. TIMI-3B is a mortality study in which patients with either non-Q-wave myocardial infarction or unstable angina with rest pain are randomly assigned to receive either tissue plasminogen activator or placebo. Results of this trial will help us in the future to determine the appropriate role of thrombolytic therapy in treating acute ischemic syndromes other than transmural myocardial infarction.