Dabigatran pharmacogenetics and secondary prevention of ischemic stroke

Due to its proven safety and effi cacy, the direct anticoagulant dabigatran is often the first choice in the secondary prevention of cardioembolic stroke in atrial fibrillation. The recommended dosage of 110 and 150 mg twice daily creates a variation in plasma levels within the therapeutic range in the treatment population. The inter-individual variability of these levels may be caused by polymorphisms of genes involved in drug transport and metabolism. Although the pharmacogenetic examination of some gene polymorphisms in the selection of drugs is currently implemented in routine clinical practice, the use of the genetic profile of patients treated with dabigatran in order to increase the safety of anticoagulant therapy is not yet part of the recommended procedures. We searched for published studies investigating polymorphisms of the CES1 and ABCB1 genes, which are involved in the absorption and metabolism of dabigatran. The most promising for clinical relevance is the rs2244613 polymorphism in the CES1 gene, which is associated with a decrease in dabigatran concentration and a lower risk of bleeding without a simultaneous increased risk of recurrence of ischemia. Carriers of the rs2244613 variant may significantly benefit from dabigatran treatment. The pharmacogenetics of dabigatran may be clinically beneficial for safer and more effective secondary prevention of cardioembolic stroke, but further clinical studies are required.