Key result
ABCB1 polymorphism rs4148738 is linked to ~8-fold higher major bleeding risk in dabigatran-treated NVAF patients.
Why the study?
Associations between genetic variants, dabigatran plasma concentrations, and clinical outcomes in patients with non-valvular atrial fibrillation needed evaluation.
Do ABCB1 and CES1 polymorphisms affect dabigatran plasma concentrations and bleeding risk in patients with non-valvular atrial fibrillation?
Cohort (n=86)
No
Do ABCB1 and CES1 polymorphisms affect dabigatran plasma concentrations and bleeding risk in patients with non-valvular atrial fibrillation?
Odds Ratio: 8.17 (95% CI 1.1–60.88)
p-value: p=0.040
In Chinese patients with NVAF, ABCB1 and CES1 polymorphisms significantly impact dabigatran trough concentrations and the risk of major bleeding.
May heighten bleeding vigilance for ABCB1 rs4148738 carriers on dabigatran; leaves open pharmacogenetic testing in Chinese NVAF.
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 c.2482-2236G>A (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 c.3435C>T (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.
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Zhu et al. (2022) conducted a cohort in Non-valvular atrial fibrillation (n=86). ABCB1 rs4148738 polymorphism vs. Noncarriers (major allele homozygotes) was evaluated on Major bleeding events (OR 8.17, 95% CI 1.10-60.88, p=0.040). The ABCB1 polymorphism rs4148738 was associated with a significantly increased risk of major bleeding events (OR 8.17) in Chinese patients with non-valvular atrial fibrillation treated with dabigatran.
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