Key result
The ABCB1 polymorphism rs4148738 was significantly associated with an increased risk for major bleeding events (OR 8.17) in Chinese patients with non-valvular atrial fibrillation treated with dabigatran.
Why the study?
This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes of dabigatran in patients with non-valvular atrial fibrillation.
Do ABCB1 and CES1 polymorphisms affect dabigatran plasma concentrations and bleeding risk in Chinese patients with non-valvular atrial fibrillation?
Cohort (n=86)
No
Do ABCB1 and CES1 polymorphisms affect dabigatran plasma concentrations and bleeding risk in Chinese patients with non-valvular atrial fibrillation?
In Chinese patients with non-valvular atrial fibrillation, the CES1 polymorphism rs8192935 is associated with increased dabigatran trough concentrations, and ABCB1 polymorphisms rs4148738 and rs1045642 are associated with an increased risk of major bleeding.
Answers are grounded in this paper and cite their sources.
May inform bleeding risk assessment for dabigatran in Chinese AF; leaves open need for prospective validation.
BACKGROUND: 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). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. 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.3435 C > 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. CONCLUSION: 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 polymorphism rs4148738 vs. Noncarriers was evaluated on Major bleeding events (OR 8.17, 95% CI 1.10-60.88, p=0.040). The ABCB1 polymorphism rs4148738 was significantly associated with an increased risk for major bleeding events (OR 8.17) in Chinese patients with non-valvular atrial fibrillation treated with dabigatran.
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