Carriers of the CES1 rs2244613 C allele had a significantly lower bleeding risk compared to AA carriers when treated with dabigatran (OR 0.62).
Systematic Review (n=13,300)
Do genetic polymorphisms impact the pharmacokinetics and bleeding risk of direct oral anticoagulants?
While genetic polymorphisms affect DOAC pharmacokinetics and bleeding risk, current evidence is insufficient to recommend routine genotype-guided dosing in clinical practice.
Effect estimate: OR 0.62 (95% CI 0.50-0.76)
p-value: p=<0.00001
Background: Direct oral anticoagulants (DOACs) exhibit considerable individual variability in effectiveness and bleeding risk, possibly due to genetic differences. This study assessed how genetic polymorphisms impact the pharmacokinetics (PK) and outcomes of DOACs. Methods: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for pharmacogenomic studies related to DOACs up to October 29, 2025. Meta-analyses were performed using RevMan 5.4 for evaluated results with ≥3 studies. Results: may affect metabolite exposure and contribute to variability in bleeding risk. Conclusion: are associated with variability in the PK and bleeding risk of DOACs. However, due to the observational nature, heterogeneity, and limited sample sizes of included studies, current evidence is insufficient to support genotype-guided dosing in clinical practice. Large prospective studies are needed to validate these findings. Systematic Review Registration: PROSPERO CRD420251240030.
Chai et al. (Tue,) conducted a systematic review in Non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) (n=13,300). Direct oral anticoagulants (DOACs) stratified by genotype vs. Different genotype groups (e.g., wild-type vs. variant carriers) was evaluated on Bleeding risk (CES1 rs2244613 C allele carriers vs AA carriers for dabigatran) (OR 0.62, 95% CI 0.50-0.76, p=<0.00001). Carriers of the CES1 rs2244613 C allele had a significantly lower bleeding risk compared to AA carriers when treated with dabigatran (OR 0.62).