Oncotarget

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

Natalia Cullell, Caty Carrera, Elena Muiño, Nuria Torres, Jerzy Krupinski and Israel Fernandez-Cadenas _

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Oncotarget. 2018; 9:29238-29258. https://doi.org/10.18632/oncotarget.25579

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Abstract

Natalia Cullell1, Caty Carrera1,2, Elena Muiño1, Nuria Torres1, Jerzy Krupinski3,4 and Israel Fernandez-Cadenas1,5

1Stroke Pharmacogenomics and Genetics, Fundació Docència i Recerca Mútua Terrassa, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain

2Neurovascular Research Laboratory, Institut de Recerca, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain

3Servicio de Neurología, Hospital Universitari Mútua Terrassa, Terrassa, Barcelona, Spain

4School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom

5Stroke Pharmacogenomics and Genetics, Institut de Recer ca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

Correspondence to:

Israel Fernandez-Cadenas, email: israelcadenas@yahoo.es

Keywords: VKA; DOACs; pharmacogenetics; GWAs; genetics

Received: October 10, 2017    Accepted: April 28, 2018    Published: June 26, 2018

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.


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