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Research

Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.38698.709572.55 (Published 19 January 2006) Cite this as: BMJ 2006;332:141

Rapid Response:

Genetic testing may help predict adverse events from warfarin

This paper on adverse events and warfarin prescribing raises the
question of whether it is possible to identify patients at a high risk of
bleeding before treatment is started[1]. Whilst some of this information
may be gleaned from the clinical history, physical examination and other
phenotypic tests, the use of warfarin in atrial fibrillation may be one
example of where pharmacogenetic testing may have a role. Whilst there
seems to be little point in performing genetic tests on patients already
stabilised on warfarin, the evidence suggests that the early phases of
treatment are the most critical and when patients are most vulnerable[2].

A systematic review and meta-analysis of studies investigating the
impact of genetic variants of the cytochrome P450 enzyme CYP2C9 and
warfarin has shown that patients with these variants require lower daily
maintenance doses and are at an increased risk of bleeding[3]. Recent
research has also shown that haplotypes of the Vitamin K epoxide reductase
gene VKORC1 can stratify patients into low- medium- and high-dose groups
and that these haplotypes vary between ethnic groups[4]. Whilst neither of
these studies is conclusive, it does perhaps provide one example where pre
-prescription pharmacogenetic testing may have a role and should be
investigated further – it may help allay the fears of patients and doctors
alike.

Reference List

1.Choudhry,N.K. et al. Impact of adverse events on prescribing
warfarin in patients with atrial fibrillation: matched pair analysis. BMJ
332, 141-145 (2006).

2.Higashi,M.K. et al. Association between CYP2C9 genetic variants and
anticoagulation-related outcomes during warfarin therapy. JAMA 287, 1690-
1698 (2002).

3.Sanderson,S., Emery,J. & Higgins,J. CYP2C9 gene variants, drug
dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic
review and meta-analysis. Genet. Med. 7, 97-104 (2005).

4.Rieder,M.J. et al. Effect of VKORC1 haplotypes on transcriptional
regulation and warfarin dose. N. Engl. J. Med. 352, 2285-2293 (2005).

Competing interests:
None declared

Competing interests: No competing interests

25 January 2006
Simon P Sanderson
Clinical Lecturer
Jon Emery, Julian Higgins, and Mark Kroese
University of Cambridge