Why the study?
Bleeding complications remain an important issue with NOACs, and ABCB1 gene variations may help individualize treatment since dabigatran and apixaban are P-glycoprotein substrates.
Do ABCB1 rs1045642 and rs4148738 variant genotypes affect non-major bleeding risk in atrial fibrillation patients treated with dabigatran or apixaban?
Do ABCB1 rs1045642 and rs4148738 variant genotypes affect non-major bleeding risk in atrial fibrillation patients treated with dabigatran or apixaban?
ABCB1 rs1045642 and rs4148738 variant genotypes are not significantly associated with non-major bleeding risk in atrial fibrillation patients treated with dabigatran or apixaban.
May support ABCB1 testing to individualize NOAC dosing in AF; leaves open whether it improves outcomes in prospective trials.
(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.
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Roşian et al. (2020) studied this question.
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