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(Circulation. 2009;120:1029-1035.)
© 2009 American Heart Association, Inc.

Arrhythmia/Electrophysiology

The First Evaluation of a Novel Vitamin K Antagonist, Tecarfarin (ATI-5923), in Patients With Atrial Fibrillation

David J. Ellis, MD, PhD; Mohammed Haris Usman, MD; Peter G. Milner, MD; Daniel M. Canafax, PharmD; Michael D. Ezekowitz, MBChB, DPHIL, FRCP

From Lankenau Institute for Medical Research, Wynnewood, Pa (M.H.U.U., M.D.E.); Mercy Catholic Medical Center, Darby, Pa (M.H.U.U.); Section of Vascular Medicine, University of Pennsylvania Health System, Philadelphia (M.H.U.U.); and ARYx Therapeutics Inc, Fremont, Calif (D.E., P.M., D.C.).

Correspondence to Michael D. Ezekowitz, MBChB, DPHIL, FRCP, Lankenau Institute for Medical Research, 100 Lancaster Ave, Wynnewood, PA 19096-3425. E-mail ezekowitzm{at}mlhs.org

Received February 4, 2009; accepted July 10, 2009.

Background— Tecarfarin (ATI-5923) is a novel oral vitamin K antagonist. Unlike warfarin, it is metabolized by esterases, escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450–mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system. Both tecarfarin and warfarin can be monitored with the international normalized ratio. We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin.

Methods and Results— This was a 6- to 12-week open-label, multicenter, phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen. Sixty-four subjects (97%) were taking warfarin at enrollment and were switched to tecarfarin. After the initial 3 weeks of tecarfarin treatment, the mean interpolated time in therapeutic range was 71.4%. Only 10.9% of patients had time in therapeutic range of <45%. Times in extreme international normalized ratio ranges of <1.5 and >4.0 were 1.2% and 1.2%, respectively. The median daily dose (for an individual patient) to maintain an international normalized ratio between 2 and 3 was 15.6 mg (range, 6 to 29 mg).

Conclusions— This is the first study of tecarfarin in patients with atrial fibrillation. It appears that tecarfarin may possess advantages over the currently available standard of care, warfarin, by improving time in therapeutic range. Adequately powered prospective trials are warranted to definitively compare tecarfarin with warfarin in clinical settings for which warfarin is indicated.

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CLINICAL PERSPECTIVE

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