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.