Pharmacogenomics of direct oral anticoagulants: a systematic review and meta-analysis

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.