Related Experiment Videos
In vivo models of arterial thrombosis and thrombolysis
1Department of Cardiovascular Research, Hoffman-La Roche, Inc., Nutley, New Jersey 07110.
Insights
Myocardial infarction (MI) treatment faces challenges, with low thrombolytic therapy use and effectiveness. New antithrombotic and profibrinolytic drugs show promise for improving patient outcomes and preventing heart attacks.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Approximately 1.5 million Americans experience myocardial infarction (MI) annually.
- Only 20% of hospitalized MI patients receive thrombolytic therapy due to risk/benefit concerns.
- Current thrombolytic therapies have limitations, including incomplete vessel reopening and acute reocclusion.
Purpose of the Study:
- To address the challenges in antithrombotic and thrombolytic therapy for myocardial infarction.
- To explore novel drug development aimed at reducing MI incidence and improving treatment efficacy.
- To investigate advancements in understanding platelet function, coagulation, and fibrinolysis.
Main Methods:
- Review of current therapeutic strategies and their limitations.
- Exploration of ongoing research and development of new pharmacological agents.
- Utilizing animal models of thrombosis for drug efficacy evaluation.
Main Results:
- Aspirin shows promising results in favorably altering treatment statistics.
- Novel drugs targeting platelet function, coagulation, and fibrinolysis are under development.
- Animal models are crucial for evaluating antithrombotic and profibrinolytic activities.
Conclusions:
- Significant challenges remain in optimizing antithrombotic and thrombolytic therapies for myocardial infarction.
- Advances in understanding hemostasis have spurred the development of promising new drug candidates.
- Further research and clinical evaluation are necessary to improve patient outcomes in MI treatment.
Abstract:
This year approximately 1.5 million Americans will undergo a myocardial infarction (MI). Of those who make it to the hospital (approximately 1.2 million), only about 20% will receive thrombolytic therapy. Multiple factors contribute to this dismaying figure, but most of them are risk/benefit-related. Moreover, of those receiving lytic therapy, the coronary arteries of as many as one-third may not reopen, and of those that do undergo coronary thrombolysis, an unacceptable fraction will experience reocclusion acutely. Thus, despite significant progress, major challenges for antithrombotic and thrombolytic therapy remain. Promising results with aspirin provide some hope that the figures above can be altered favorably. Efforts are under way in industry and academia to develop drugs to accomplish one or more of the following: lower the incidence of MI, prevent the development of unstable angina or retard its progression to frank MI, increase the inclusion window for lytic therapy, raise the percentage of patients undergoing successful thrombolysis, and maintain coronary patency. During the period that thrombolytic agents have come into vogue important advances have been made in our understanding of platelet function, coagulation, and the endogenous fibrinolytic system. These have spurred the development of novel drugs, such as platelet fibrinogen receptor antagonists, plasminogen activators, and inhibitors of factor IIa (thrombin) and XIIIa. Evaluation of these agents for their antithrombotic or profibrinolytic activity requires relevant animal models of thrombosis. Despite appropriate concerns about their clinical relevance, these models bridge the wide gap between test tube assays of aggregation or coagulation and humans.