The National Heart, Lung, and Blood Institute (NHLBI), in collaboration with the Office of Dietary Supplement (ODS), the NIH Clinical Center (CC), the National Center for Complementary and Alternative Medicine (NCCAM), the National Institute of Neurological Disorders and Stroke (NINDS), NIH Foundation, and the Office of Rare Diseases (ORD) at the National Institutes of Health (NIH), is convening a national conference to increase our understanding of the potential for dietary supplements to interfere with hemostasis and antithrombotic therapies. The conference will take place in Masur Auditorium at the NIH Clinical Center in Bethesda and will:

• Review the effects of dietary supplements on hemostasis and antithrombotic therapies
• Develop strategies to raise awareness among patients and practitioners about the use of dietary supplements
• Formulate a framework for developing a clinical guideline for dietary supplement use in patients on antithrombotic therapies
• Promote integration of new knowledge on the subject into media platforms including NIH internet resources and web-based home monitoring systems for antithrombotic therapies
• Identify gaps in our current knowledge
• Formulate a research agenda

Cardiovascular and cerebrovascular diseases are the leading causes of death in the United States. An estimated 4 million patients receive long-term antithrombotic therapies (anticoagulants with or without antiplatelet agents) and this number is expected to increase. Additionally, surveys suggest that dietary supplements may be used in 12-24% of the general population. Recently, 43% of VA ambulatory care patients reported using one or more dietary supplements, with up to 45% of supplement users having potential drug-dietary supplement interactions. Non-prescription drugs, vitamins, minerals, botanicals, homeopathies, and other complementary and alternative therapies are being promoted, which has resulted in an increased use of these products among the general population. Because antithrombotic therapies have narrow therapeutic windows, they must be monitored so that patients are not put at risk for thromboembolic or hemorrhagic complications. Unfortunately, studies have found that patients under report the use of dietary supplements and non-prescription medications to their caregivers.

To date, there have been few systematic examinations of the prevalence of non-prescription medications and their ingredients, which may either enhance or diminish effects of prescribed antithrombotic (anticoagulant or antiplatelet) agents. According to the Natural Medicines Comprehensive Database, approximately 180 dietary supplements have the potential to interact with warfarin and more than 120 may interact with aspirin, clopidogrel, or dipyridamole. They include anise and Dong Quai (anticoagulants effects); omega 3-fatty acids in fish oil, ajoene in garlic, ginger, Ginko, and vitamin E (antiplatelet properties); Fucus (heparin like activity); Danshen (antithrombin III-like activity and anticoagulant bioavailability), and St. John’s Wort and American Ginseng (interference with drug metabolism). Others supplements, such as high dose vitamin E (vitamin K antagonist); Alfalfa (high vitamin K content); and Coenzyme Q10 (vitamin K-like activity) may affect blood clotting, which is dependent on vitamin K.

Drug interactions with herbal and other dietary supplements are much more difficult to capture, characterize and predict because these products are not required to undergo FDA review or approval prior to their marketing. They also do not need to meet the same quality standards as do prescription drugs. Manufacturers are responsible for showing that they are safe and efficacious. Based on pharmacodynamic and pharmacokinetic properties of the commercially available supplements and herbal remedies, the potential for interactions is high. Although practitioners are encouraged to report such interactions to the FDA, published case reports of interactions with the most widely used dietary supplements are limited. Clinical guidance for practitioners who prescribe antithrombotic medications and patients who receive them with respect to dietary supplement use is lacking. This conference seeks to raise awareness among practitioners about the potential harm or benefit of dietary supplements to patients receiving long-term antithrombotic therapies.

Although a variety of dietary supplements may affect hemostasis, very few are absolutely contraindicated in people with bleeding disorders or on antithrombotic therapies. The medical community would benefit from evaluation and information on these supplements and their harm or benefit to antithrombotic therapies.

To address this issue, the conference will bring together a broad spectrum of experts to discuss the current knowledge, review regulatory and safety issues, share recent clinical trial findings, and identify opportunities for further research. Attendance will include stakeholders from academies and industries, representatives from Institutes and Centers within NIH, patient advocates, and members of Federal and non-governmental regulatory and standards-setting organizations.

Charge to the Panel

• Identify factors that determine the beneficial or adverse effects of dietary supplements on hemostasis and antithrombotic therapies
• Identify evidence that supports various effects of dietary supplements on hemostasis and antithrombotic therapies
• Identify public health concerns about use of various dietary supplements; determine how they can be used safely by patients on antithrombotic therapies
• Identify gaps in our knowledge on interactions of dietary supplements with antithrombotic therapies, and determine priorities of future research
• Determine a framework for developing clinical guidelines on prescribing dietary supplements for patients on antithrombotic therapies and on recognizing, preventing, and monitoring their adverse effects.

Planned Outcomes: The proceedings will be published in a suitable medical journal to enhance public awareness, encourage standardization of methods used to assess the adverse effects of dietary supplements in individuals on antithrombotic therapies, and identify research needs.

Co-Sponsors: CC, NCCAM, NINDS, ODS, ORD, and Foundation for the NIH

Potential Participants: Stakeholders from academies and industries, representatives from Institutes and Centers within NIH, patient advocates, and members of other Federal and non-governmental regulatory and standards-setting organizations.

Organizer/Program Contact: Ahmed A.K. Hasan, M.D., Ph.D., Medical Officer/Program Administrator, Thrombosis and Hemostasis Scientific Research Group (SRG), Division of Blood Diseases and Resources (DBDR), NHLBI, NIH, Phone: 301-435-0064, Fax: 301-480-1046,

E-mail: hasana@nhlbi.nih.gov

Outlines of the Agenda

Thursday, January 13, 2005

Session I: Dietary Supplements That Affect Hemostasis and Antithrombotic Therapies

• Interactions of dietary supplements with hemostasis
  
  
• Epidemiology and inventory of supplements use by patients on antithrombotic therapies

Session II: Biochemical Effects of Dietary Supplements on Hemostasis

• Mechanisms of various effects of the supplements on hemostasis and antithrombotic therapies

Session III: Clinical Data on Supplements Affecting Hemostasis and Antithrombotic Therapies

• Evidence-based inventory of dietary supplements that are known to interact with anticoagulant, antiplatelet, and fibrinolytic agents

Friday, January 14, 2005

Session IV: New Tools and Methodologies for Research and Clinical Practice

• Predicting and preventing adverse herb-drugs interactions
  
  
• Challenges in monitoring and best practices for clinical trial design involving supplements

Session V: Panel of Experts: Opinions and Research Priorities

• Gaps in our current knowledge for formulating a research agenda in the area

Session VI: Public Health Concerns: Facts, Fictions, and Gaps in Knowledge

• Public health concerns regarding supplement use while on antithrombotic therapies

Session VII: Dialogue with Patient Care Organizations

• Discussion on current practices and guidelines involving supplements that may affect hemostasis and antithrombotic therapies