A randomised, double blind comparison of tecarfarin, a novel vitamin K antagonist, with warfarin. The EmbraceAC Trial.

Abstract:

: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.

journal_name

Thromb Haemost

authors

Whitlock RP,Fordyce CB,Midei MG,Ellis D,Garcia D,Weitz JI,Canafax DM,Albrecht D,Milner PG

doi

10.1160/TH15-11-0910

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

241-50

issue

2

eissn

0340-6245

issn

2567-689X

pii

15-11-0910

journal_volume

116

pub_type

杂志文章,多中心研究,随机对照试验
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    pub_type: 杂志文章,meta分析

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    pub_type: 杂志文章,随机对照试验

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    doi:

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    pub_type: 临床试验,杂志文章

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    pub_type: 杂志文章,已发布勘误

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    doi:

    authors: Kesteven PJ,Holland LJ,Lawrie AS,Savidge GF

    更新日期:1984-08-31 00:00:00