Key result
SLCO1B1 variant linked to ~5.5-fold higher bleeding risk in edoxaban-treated patients.
Why the study?
Because SLCO1B1 encodes the transporter OATP1B1, which can influence edoxaban pharmacokinetics and pharmacodynamics, polymorphisms in SLCO1B1 may affect patient response.
Do SLCO1B1 genetic polymorphisms affect bleeding risk in patients treated with edoxaban?
Observational (n=159)
Yes
Do SLCO1B1 genetic polymorphisms affect bleeding risk in patients treated with edoxaban?
Effect estimate: OR 5.48 (95% CI 1.75-17.23)
Absolute Event Rate: 23.8% vs 6.8%
p-value: p=<0.01
Genetic polymorphisms in SLCO1B1 and ABCB1 significantly influence the risk of bleeding complications in patients taking edoxaban, suggesting a potential role for pharmacogenomic testing to personalize DOAC therapy.
SLCO1B1 variant associated with higher edoxaban bleeding risk; leaves open whether pharmacogenomic testing improves outcomes.
Since SLCO1B1 encodes the uptake transporter OATP1B1, which can influence the pharmacokinetic and pharmacodynamic profiles of edoxaban, polymorphisms in SLCO1B1 may affect the edoxaban response. This study aimed to investigate the association between SLCO1B1 gene polymorphisms and the bleeding risk in patients receiving edoxaban. We genotyped 10 single-nucleotide polymorphisms (SNPs) from the SLCO1B1 gene in patients receiving edoxaban. We also analyzed rs3842 of ABCB1 as a confounder. The odds ratio (OR) and adjusted OR (AOR) were calculated from univariate and multivariable analysis, respectively. The area under the receiver operating characteristic curve (AUROC) was constructed for the discrimination of the model. A total of 159 patients receiving edoxaban were analyzed. Overdose and rs4149056 showed significant association with bleeding complications by around 11- and 5.5-fold, respectively. Additionally, patients with the rs4149057 variant allele (C) had a 3.9-fold increased bleeding risk compared with wild-type homozygote carriers (TT), whereas rs2306283 variant homozygote (GG) carriers had a 0.27-fold reduced bleeding risk compared with wild-type allele (A) carriers. Patients with the variant-type homozygote (CC) of ABCB1 rs3842 had a higher bleeding risk than T allele carriers (AOR = 5.3 and 5.9). The final models for multivariable analyses were acceptable based on the AUROC values (> 0.70). These findings may help predict bleeding risk in patients taking edoxaban and help personalize treatment.
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Han et al. (2023) conducted an observational in Atrial fibrillation or secondary stroke prevention (n=159). SLCO1B1 rs4149056 variant allele (C) vs. SLCO1B1 rs4149056 wild-type homozygote (TT) was evaluated on One-year major bleeding event and clinically relevant non-major bleeding (CRNMB) (OR 5.48, 95% CI 1.75-17.23, p=<0.01). The SLCO1B1 rs4149056 variant allele (C) increased the risk of bleeding complications by 5.5-fold compared to wild-type carriers in patients treated with edoxaban.
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