Review ArticleNew antithrombotics: The impact on global health care
Section snippets
Background and epidemiology of thromboembolism
Arterial thromboembolism (ATE) and venous thromboembolism (VTE) are leading causes of morbidity and mortality world-wide [1]. While ATE typically forms under high shear conditions of blood flow and consists of platelets bound by small amounts of fibrin, VTE forms under low shear conditions [2]. In the US alone, it is estimated that over 850,000 acute myocardial infarctions (MI) occur annually, with an 18% and 35% recurrence rate within 6 years for men and women, respectively [3]. ATE is the most
Antiplatelet therapy
A number of antiplatelet agents are in advanced stages of development. These medications primarily target adenosine diphosphate (ADP), thromboxane A2, or thrombin receptors on the platelet surface (Fig. 1, Fig. 2) [1], [6]. A majority of the ADP receptor antagonists specifically target P2Y12 while the thrombin receptor antagonists primarily target protease activated receptor-1 (PAR-1) [1].
Prasugrel is a new oral ADP receptor antagonist (P2Y12 platelet inhibitor) that has been recently approved
Impact of new agents
New agents approved for use will likely have higher drug acquisition costs than current strategies. Economic analyses will be helpful to determine if overall costs are cost- neutral or cost-dominant due to reduced need for monitoring, or improved efficacy and safety. Preliminary cost-analyses appear to favor new agents over current standards of care, despite higher acquisition costs, although further analysis is needed [37], [38], [39], [40], [41]. The market to replace warfarin with new
Current controversies
Key controversies that remain are:
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Superiority of agents
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Optimal duration of prophylaxis
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Will patients with more than one indication for antithrombotic therapy require dual or triple antithrombotics with the new, more potent anticoagulants?
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Future of biosimilars
Without head-to-head clinical trials, the differences in new agents, such as half-lives, drug interactions, safety in special populations (e.g. frail elderly, renal, obesity, etc), will play an important role in which agent takes the lead in
Conclusion
ATE and VTE continue to have a tremendous impact on international health systems with a huge unmet need for new medical and pharmacologic improvements. The antithrombotic market will have many additions in the near future and education surrounding these new agents and appropriate use will be critical. A balanced approach between industry, the FDA, key thrombosis organizations, consumers, and health care systems would be helpful in developing both consensus statements and education on
Dedication
We would like to dedicate this publication to the North American Thrombosis Forum (NATF) and the patients who have lost their lives to, or been harmed from, thromboembolism. The NATF strives to reduce both morbidity and mortality associated with thromboembolism.
Conflict of interest statement
Within the last year, Dr. Mahan has received honoraria as a consultant and speaker from Eisai and Sanofi-Aventis Pharmaceuticals and as a consultant from Polymedix and Leo Pharmaceuticals. He has also received travelling fellowship funds from the North American Thrombosis Forum. Dr. Mahan is an unpaid consultant for Johnson and Johnson Pharmaceutical Research & Development and Ortho-McNeil Janssen Scientific Affairs.
Acknowledgement
NATF coordinated a roundtable discussion with experts on September 26th, 2010. The following are some key points discussed during this roundtable session.
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