Ask Dr. Stephan Moll

These questions have been submitted by folks on the mailing list and answered by Dr. Moll, Director of the Thrombophilia Program at the Carolina Cardiovascular Biology Center, Department of Medicine, Division of Hematology-Oncology, UNC Chapel Hill (North Carolina, USA). Why am I doing this?

2. Alternatives to coumadin^® (= warfarin)

Are there any blood thinning medications other than warfarin (coumadin®) that can be taken as a tablet?"

None are available yet. Several are in development, but probably about four years away from coming onto the market.

A discussion plus a table of various drugs. The drug Exanta® (Ximelagatran) produced by Astra-Zeneca.was temporarily available in Europe between 2005 and 2006, but was voluntarily withdrawn from the market on February 14, 2006.

The new anticoagulants in development have several promising features: They

• can be given orally (once or twice a day),
• do not appear to need monitoring of their blood thinning effects, i.e. it have a very predictable blood-thinning effect - "one dose fits all",
• are typically immediately active, thus initial heparin therapy in acute DVT/PE will not be necessary,
• have no interaction with vitamin K in the diet, thus patients can eat what they want,
• have a short half-life (thus, can be discontinued at times of surgery 12-24 hours before surgery).

Exanta®'s main downside was that it caused liver test elevation in some patients. This led the FDA to not approve the drug in the U.S. on Oct 11, 2004 and led to withdrawal of the drug from the worldwide market on Feb. 14, 2006. Diligent attention is paid with all the new drugs in development as to what their liver toxicity might be an close testing for liver test elevations are being done in the clinical trials.

References:

1. Francis CW et al.: Comparison of Ximelagatran with Warfarin for the Prevention of Venous Throbmoembolism after Total Knee Relacement. New England Journal of Medicine; Oct 30, 2003:349:1703-12.
2. Colwell CW et al: Comparison of Ximelagatran, an Oral Direct Throbmin Inhibitor, with Enoxaparin for the Prevention of Venous Thromboembolism Following Total Hip Replacement. J Thromb Haemost; Nov 2003.
3. Francis CW et al.: Efficacy and Safety of the oral direct thrombin inhibitor Ximelagatran Compare with Current Standard Theray for Acute Symptomatic Deep Vein Thrombosis, with or without Pulmonary Embolism: The THRIVE Treatment Study. Blood 2003;102:abstract 7.
4. Schulman S et al.: Secondary Prevention of Venous Thromboembolism with the Oral Direct Thrombin Inhibitor Ximelagatran (THRIVE III trial"; New England Journal of Medicine;Oct 30, 2003;349:1713-21.
5. Wallentin L et al.: Oral Ximelagatran for Secondary Prophylaxis after Myocardial Infarction: the ESTEEM randomized controlled trial. Lancet; Sept 6,2003;362:789-97.

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