Introduction
Non-valvular atrial fibrillation (NVAF) is the most common cardiac
arrhythmia and is associated with an increased risk of ischemic stroke
globally1,2. Dabigatran etexilate (DE) is a novel
non-vitamin K antagonist oral anticoagulant (NOAC) that is widely used
in NVAF patients to prevent the formation of
thrombus3,4. DE was given in fixed-dose treatments
without coagulation monitoring, which was shown to be more effective and
safer for patients than vitamin K antagonists3.
The effect of genetic factors on the pharmacokinetics of active
dabigatran metabolites has been investigated in several
studies5-10. Furthermore, dabigatran was also observed
to cause clinical bleeding, which is closely associated with genetic
polymorphisms6,7,10. The major genetic determinants
involved in the metabolism of DE are the carboxylesterase 1 (CES1) and
ATP binding cassette subfamily B member 1 (ABCB1)
genes11-13. Single nucleotide polymorphisms (SNPs) of
CES1 and ABCB1 have shown a significant effect on dabigatran dosing
variations and their safety parameters.
However, few studies have examined Asian populations that differ in the
risk of bleeding and genetic polymorphisms under anticoagulant therapy
conditions, and the genetic impact on dabigatran PK/PD in Chinese or
Asian populations remains unclear12. The only study
conducted at Zhongshan Hospital indicated the effect of genetic
associations of dabigatran along with the bleeding risk for individuals,
but it failed to elucidate major bleeding and thromboembolic events of
this variability due to the small number of patients enrolled in the
study6.
To date, very few pharmacogenetic studies on dabigatran in Asian
patients have been published, and the evidence level of these
associations is low. Therefore, the purpose of our study was to identify
the impact of gene polymorphisms on the plasma concentration and
clinical events of dabigatran in Chinese patients treated with DE for
NVAF.