Key result
ABCG2 rs3114018 A allele linked to ~2.2-fold higher bleeding risk on apixaban or rivaroxaban.
Why the study?
DOACs carry a risk of bleeding complications, and breast cancer resistance protein encoded by ABCG2 is an efflux transporter of apixaban and rivaroxaban.
Does the ABCG2 rs3114018 gene polymorphism increase the risk of bleeding complications in patients with nonvalvular atrial fibrillation treated with apixaban or rivaroxaban?
Case-Control (n=293)
Yes
Does the ABCG2 rs3114018 gene polymorphism increase the risk of bleeding complications in patients with nonvalvular atrial fibrillation treated with apixaban or rivaroxaban?
Odds Ratio: 2.188 (95% CI 1.156–4.142)
p-value: p=0.016
Genetic profiling for ABCG2 and ABCB1 polymorphisms may help predict bleeding risk and optimize individual treatment strategies for patients taking apixaban or rivaroxaban.
May warrant caution in ABCG2 A allele carriers on apixaban or rivaroxaban; leaves open prospective validation before guiding therapy.
Purpose: Direct oral anticoagulants (DOACs) are widely used for stroke prevention in atrial fibrillation. However, they have a bleeding complication. Breast cancer resistance protein, encoded by ABCG2 , is known to be an efflux transporter of apixaban and rivaroxaban among DOACs. This study aimed to investigate the association between gene variants and bleeding complications during treatment with ABCG2 substrates (apixaban and rivaroxaban). Patients and Methods: Patients treated with apixaban and rivaroxaban were enrolled from June 2018 to December 2021. Five single nucleotide polymorphisms (SNPs) of ABCG2 were selected. Previously studied genes ( ABCB1, CYP3A4 , and CYP3A5 ) were further analyzed as possible confounders. Finally, a total of 16 SNPs were examined in this case–control study. The outcome was defined as major bleeding and clinically relevant non-major bleeding. Two models were constructed using the multivariable analysis. Results: Among 293 patients, 64 were cases. The mean age of the patients was 68.8 years, and males comprised 62.5% of the study population. Model I revealed that a history of bleeding, concurrent use of proton pump inhibitor (PPI), ABCG2 rs3114018, and ABCB1 rs1045642 were significantly associated with bleeding complications; the AORs (95% CI) were 6.209 (2.210– 17.442), 2.385 (1.064– 5.349), 2.188 (1.156– 4.142), and 3.243 (1.371– 7.671), respectively. Model II showed that modified HAS-BLED score, concurrent use of PPI, ABCG2 rs3114018, and ABCB1 rs1045642 were significantly associated with bleeding complications. Conclusion: The modified HAS-BLED score, a history of bleeding, concurrent use of PPI, ABCG2 rs3114018, and ABCB1 rs1045642 were significantly associated with the risk of bleeding complications in patients on apixaban and rivaroxaban, after adjusting for other confounders. These findings can be used to develop individualized treatment strategies for patients taking apixaban and rivaroxaban.
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Kim et al. (2023) conducted a case-control in Nonvalvular atrial fibrillation (n=293). ABCG2 rs3114018 A allele vs. ABCG2 rs3114018 CC genotype was evaluated on Bleeding complications (major bleeding and clinically relevant non-major bleeding) (AOR 2.188, 95% CI 1.156-4.142, p=0.016). The ABCG2 rs3114018 A allele was significantly associated with an increased risk of bleeding complications in patients taking apixaban or rivaroxaban compared to the CC genotype (AOR 2.188, 95% CI 1.156-4.142).
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