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Review
. 2018 Jun 26;9(49):29238-29258.
doi: 10.18632/oncotarget.25579.

Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants

Natalia Cullell  1 , Caty Carrera  1   2 , Elena Muiño  1 , Nuria Torres  1 , Jerzy Krupinski  3   4 , Israel Fernandez-Cadenas  1   5
Affiliations
Review

Pharmacogenetic studies with oral anticoagulants. Genome-wide association studies in vitamin K antagonist and direct oral anticoagulants

Natalia Cullell et al. Oncotarget. .

Abstract

Oral anticoagulants (OAs) are the recommended drugs to prevent cardiovascular events and recurrence in patients with atrial fibrillation (AF) and cardioembolic stroke. We conducted a literature search to review the current state of OAs pharmacogenomics, focusing on Genome Wide Association Studies (GWAs) in patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). VKAs: Warfarin, acenocoumarol, fluindione and phenprocoumon have long been used, but their interindividual variability and narrow therapeutic/safety ratio makes their dosage difficult. GWAs have been useful in finding genetic variants associated with VKAs response. The main genes involved in VKAs pharmacogenetics are: VKORC1, CYP2C19 and CYP4F2. Variants in these genes have been included in pharmacogenetic algorithms to predict the VKAs dose individually in each patient depending on their genotype and clinical variables. DOACs: Dabigatran, apixaban, rivaroxaban and edoxaban have been approved for patients with AF. They have stable pharmacokinetics and do not require routine blood checks, thus avoiding most of the drawbacks of VKAs. Except for a GWAs performed in patients treated with dabigatran, there is no Genome Wide pharmacogenomics data for DOACs. Pharmacogenomics could be useful to predict the better clinical response and avoid adverse events in patients treated with anticoagulants, identifying the most appropriate anticoagulant drug for each patient. Current pharmacogenomics data show that the polymorphisms affecting VKAs or DOACs are different, concluding that personalized medicine based on pharmacogenomics could be possible. However, more studies are required to implement personalized medicine in clinical practice with OA and based on pharmacogenetics of DOACs.

Keywords: DOACs; GWAs; VKA; genetics; pharmacogenetics.

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Conflict of interest statement

CONFLICTS OF INTEREST Nothing to disclose.

Figures

Figure 1
Figure 1. Flow diagram in the selection of articles included in the review
Figure 2
Figure 2. Mechanism of action of the different OAs and polymorphic genes associated with OAs response
(A) Mechanism of action of VKAs. (B) Mechanism of action of DOAC. *Genes with polymorphisms associated with OAs variation in GWAs.
See this image and copyright information in PMC

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