| | Oral direct thrombin inhibitors are under investigation as a replacement for vitamin K antagonists, which for nearly a half century have been the only oral anticoagulant drugs available for clinical use. However, the first in this new class of drugs to reach large scale clinical trials, ximelagatran (Exanta, AstraZeneca), was recently denied approval in the United States by the Food and Drug Administration (FDA). Ximelagatran’s new drug application (NDA) was submitted for stroke prevention in patients with atrial fibrillation, prevention of venous thromboembolism (VTE) in patients undergoing knee replacement surgery, and for long-term secondary prevention of VTE following standard acute therapy.
In this interview with ThrombosisClinic.com, Dr Jonathan Halperin addresses key issues surrounding ximelagatran clinical trials and the decision by the FDA not to grant NDA approval. Dr Halperin is Professor of Medicine at the Mount Sinai School of Medicine and Director of Cardiology and Clinical Services at the Mount Sinai Medical Center in New York City. He served as co-chairman of the executive committee governing the SPORTIF clinical studies, including the SPORTIF III and V pivotal clinical trials for ximelagatran in atrial fibrillation.
References
- Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, et al; EXULT A Study Group. Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee replacement. N Eng J Med. 2003;349:1703-1712.
- Olsson SB; Executive Steering Committee on behalf of the SPORTIF III Investigators: Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomized controlled trial. Lancet. 2003;362:1691-1698.
- Halperin JL on behalf of the SPORTIF-V Investigators. SPORTIF V: A long-term randomized trial comparing ximelagatran with warfarin for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation [abstract]. Circulation. 2003;108:2723.
- Schulman S, Wahlander K, Lundstrom T, Clason SB, Eriksson H; THRIVE III Investigators. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. N Engl J Med. 2003;349:1713-1721.
Note:
For the purpose of clarity, the transcript of the interview has been slightly modified. All changes have been made under the direction of and with the express approval of Dr Jonathan L. Halperin.
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