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Thromb Haemost 2016; 116(02): 241-250
DOI: 10.1160/TH15-11-0910
Coagulation and Fibrinolysis
Schattauer GmbH

A randomised, double blind comparison of tecarfarin, a novel vitamin K antagonist, with warfarin

The EmbraceAC Trial
Richard P. Whitlock
1   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
Christopher B. Fordyce
2   Duke Clinical Research Institute, Durham, North Carolina, USA
,
Mark G. Midei
3   Armetheon Incorporated, Milpitas, California, USA
,
Dave Ellis
4   Durect Corporation, Cupertino, California, USA
,
David Garcia
5   Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington, USA
,
Jeffrey I. Weitz
6   Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada
,
Daniel M. Canafax
7   Theravance Biopharma, South San Francisco, California, USA
,
Detlef Albrecht
3   Armetheon Incorporated, Milpitas, California, USA
,
Peter G. Milner
3   Armetheon Incorporated, Milpitas, California, USA
› Institutsangaben Financial support: Funding for this study was provided entirely by ARYx Therapeutics, Inc, Fremont, CA, USA.
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Publikationsverlauf

Received: 30. November 2015

Accepted after major revision: 05. April 2016

Publikationsdatum:
09. November 2017 (online)

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Summary

Tecarfarin is a novel vitamin K antagonist that is metabolised by carboxyl estererase, thereby eliminating the variability associated with cytochrome-mediated metabolism. EmbraceAC was designed to compare the quality of anticoagulation with tecarfarin and warfarin as determined by time in therapeutic range (TTR). In this phase 2/3 randomised and blinded trial, 607 patients with indications for chronic anticoagulation were assigned to warfarin (n=304) or tecarfarin (n=303). Dosing of study drugs was managed by a centralised dose control centre, which had access to genotyping. The primary analysis tested superiority of tecarfarin over warfarin for TTR. Patients were recruited between May 12, 2008 and May 12, 2009. TTR with tecarfarin and warfarin were similar (72.3% and 71.5%, respectively; p=0.51). In those taking CYP2C9 interacting drugs, the TTR on tecarfarin (n=92) was similar to that on warfarin (n=87, 72.2% and 69.9%, respectively; p=0.15). In patients with mechanical heart valves, the TTR of tecarfarin (n=42) was similar to that of warfarin (n=42, 68.4% and 66.3%, respectively; p=0.51). The same was true for the TTR in patients with any CYP2C9 variant allele and on CYP2C9-interacting drugs (tecarfarin, n=24, 76.5% vs warfarin, n=31, 69.5%; p=0.09). There was no difference in thromboembolic or bleeding events. In conclusion, superiority of tecarfarin over warfarin for TTR was not demonstrated. The TTR with tecarfarin was similar to that with well-controlled warfarin and tecarfarin appeared to be safe and well tolerated with few major bleeding and no thrombotic events. Favourable trends in certain subpopulations make tecarfarin a promising oral anticoagulant that deserves further study.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Anticoagulation - warfarin - tecarfarin - CYP2C9

 

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