The impact of ABCB1 and CES1 polymorphisms on the safety of dabigatran
in patients with non-valvular atrial fibrillation
Abstract
Aims: This study aimed to analyze associations between genetic variants
and plasma concentrations along with clinical outcomes in dabigatran in
patients with non-valvular atrial fibrillation (NVAF). Methods: We
conducted a prospective study and enrolled NVAF patients treated with
dabigatran in the real world. A total of 86 patients treated with 110 mg
DE twice daily were recruited for this study. Blood samples were
obtained from each patient and used for genotyping and determination of
plasma dabigatran concentration. All bleeding and thromboembolic
complications were recorded during the 1.5 years of follow-up. Results:
Eighty-three patients provided samples at the trough plasma level of
dabigatran, and 58 patients provided samples at the peak plasma level of
dabigatran. There was a significant association between the CES1 SNP
rs8192935 and trough plasma concentrations of dabigatran (P=0.013). The
ABCB1 SNP rs4148738 was associated with major bleeding events in the
addictive model (P=0.046, OR=3.29) and dominant model (P=0.040,
OR=8.17). Additionally, the ABCB1 SNP rs1045642 was associated with the
incidence of major bleeding events in the addictive model (P=0.043,
OR=3.34) and dominant model (P=0.046, OR=7.77). However, no significant
associations were found between all the SNPs and the incidence of minor
bleeding events. Conclusions: Our results indicated that the CES1
polymorphism rs8192935 was associated with trough plasma concentrations
of dabigatran. Carriers of the G allele had increased trough plasma
concentrations of dabigatran compared to noncarriers. The ABCB1
polymorphisms rs4148738 and rs1045642 were associated with an increased
risk for major bleeding events for the first time in a Chinese
population.