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Thrombolytic therapy for acute myocardial infarction. A review
C B Granger1, R M Califf, E J Topol
1GUSTO Coordinating Center, Duke University Medical Center, Durham, NC 27710.
Insights
Thrombolytic therapy effectively treats acute myocardial infarction, reducing mortality. However, newer agents like tissue plasminogen activator (tPA) haven't shown superior survival benefits over streptokinase, necessitating new evaluation methods.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Thrombolytic therapy is standard for acute myocardial infarction (AMI).
- Thrombosis is key in AMI pathogenesis, recognized in the 1980s.
- Several thrombolytic agents, including streptokinase, urokinase, tPA, and anistreplase, have been developed.
Purpose of the Study:
- To review the efficacy and clinical outcomes of thrombolytic agents in AMI.
- To assess the benefits and limitations of various thrombolytic therapies.
- To highlight the need for improved evaluation methods for new thrombolytic agents.
Main Methods:
- Review of large, randomized clinical trials on thrombolytic therapy for AMI.
- Analysis of data on clot lysis, coronary patency, mortality reduction, and adverse effects.
- Comparison of different thrombolytic agents, including streptokinase and tPA.
Main Results:
- Thrombolytic therapy reduces mortality in ST-elevation AMI within 6-12 hours, with a 0.5% risk of intracranial hemorrhage.
- Agents like tPA show fibrin specificity and rapid lysis but not superior survival benefits compared to streptokinase.
- Improved early patency and left ventricular function do not consistently correlate with improved survival.
Conclusions:
- Thrombolytic therapy is effective but the paradigm for its use in AMI requires re-evaluation.
- Current evaluation methods may not fully capture the clinical benefit of new thrombolytic agents.
- Further development of evaluation methods for novel thrombolytic drugs is essential.
Abstract:
In the past 10 years, thrombolytics have become standard therapy for acute myocardial infarction. Although the ability of streptokinase to lyse clot was first recognised in the 1930s, thrombolytic therapy was not used to treat acute myocardial infarction until the early 1980s, when the importance of thrombosis in the pathogenesis of acute infarction was fully recognised. In addition to streptokinase and urokinase, recombinant human tissue plasminogen activator (tPA) and anistreplase were developed and widely used in the 1980s. Saruplase (prourokinase) and BM-06022 (recombinant plasminogen activator) have also undergone human clinical studies. All of these agents are effective at achieving clot lysis and coronary patency. Large, randomised clinical trials have demonstrated that thrombolytic therapy reduces mortality in patients with ST elevation treated within the first 6 to 12 hours of acute infarction, with an approximately 0.5% risk of intracranial haemorrhage. Recent data have more clearly identified which patients benefit from thrombolytic therapy. Efforts have been made to improve the speed of reperfusion, decrease reocclusion, simplify administration and reduce adverse effects. The characteristics of fibrin specificity and more rapid clot lysis with tissue plasminogen activator have not yet been translated into overall clinical benefit compared with the less expensive streptokinase. The lack of close association of improved early patency and improved global left ventricular function with improved survival challenges the very paradigm which led to the use of thrombolytic therapy for acute myocardial infarction. The need for development of additional methods for evaluation of new thrombolytic agents is evident.