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Current anticoagulant therapy--unmet clinical needs
1Department of Medicine, Hamilton Civic Hospitals Research Centre, and McMaster University, Hamilton, Ontario, Canada. jhirsch@thrombosis.hhscr.org
Thrombosis Research
|June 24, 2003
Summary
New anticoagulants offer improved safety and ease of use over warfarin and heparin. These novel agents target various steps in the coagulation pathway, aiming to overcome the limitations of traditional therapies.
Area of Science:
- Pharmacology
- Hematology
- Drug Development
Background:
- Heparin and warfarin have been mainstays for over 50 years but have significant drawbacks.
- Warfarin requires frequent monitoring due to unpredictable effects and drug/food interactions.
- Heparin and low-molecular-weight heparin (LMWH) necessitate parenteral administration, with heparin requiring monitoring.
Purpose of the Study:
- To review the development of novel anticoagulants.
- To compare the mechanisms of action and properties of new agents.
- To assess the potential of these new drugs to replace current anticoagulants.
Main Methods:
- Review of anticoagulants targeting various coagulation pathway steps.
- Analysis of approved direct thrombin inhibitors (DTIs) and a synthetic pentasaccharide.
- Evaluation of agents in Phase III studies, including activated protein C (APC) and tissue factor pathway inhibitor (TFPI).
Main Results:
- Development of anticoagulants targeting factor VIIa/tissue factor, FIXa, FXa, protein C pathway, and thrombin.
- Three DTIs (hirudin, bivalirudin, argatroban) and synthetic pentasaccharide (Arixtra) are clinically approved.
- Several other novel agents have advanced to Phase III clinical trials.
Conclusions:
- New anticoagulants offer potential advantages in efficacy, safety, and ease of use.
- These agents represent a significant advancement in managing thromboembolic conditions.
- Further review is needed to understand their full potential to replace existing therapies.