Genetic Testing Before Anticoagulation? A Systematic Review of Pharmacogenetic Dosing of Warfarin

Division of Hospital Medicine, University of California, Box 0131, 533 Parnassus Ave, San Francisco, CA 94143-0131, USA
Journal of General Internal Medicine (Impact Factor: 3.45). 05/2009; 24(5):656-664. DOI: 10.1007/s11606-009-0949-1


BackgroundGenotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all
dosing method.

ObjectiveThe objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing
the occurrence of serious bleeding events and over-anticoagulation.

Data SourcesThe authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language
restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a “standard” dose
control algorithm in adult patients taking warfarin for the first time.

Review MethodsTwo reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were
major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included
minor bleeding, thrombotic events and other measures of anticoagulation quality.

ResultsThree of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms,
length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference
in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary
or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07)
in the pharmocogenetic arm.

ConclusionsWe did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical
trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice.


Available from: Jeffrey A Tice, Sep 26, 2014
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    • "From our systematic review there is little evidence to use genotyping, which conflicts with the recent FDA statement, and the change in labelling for warfarin therapy, which states: "...lower initiation doses should be considered for patients with certain genetic variations in CYP2C9" [27]. Our findings are in accordance with a recent systemic review [28] that showed there are only three randomized trials of genotyping; which are underpowered, and with significant heterogeneity between trials results. In addition, a recent editorial by Ansell notes "most problematic is that the intervention arm of each trial is considerably different" [27]. "
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