Pharmacogenomic Profiling in Antithrombotic Therapy for Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major risk factor for ischemic stroke. Antithrombotic therapy remains central to stroke prevention in AF, yet interindividual variability in drug response poses challenges for efficacy and safety, particularly regarding bleeding risk and subtherapeutic anticoagulation. Pharmacogenomics offers a precision medicine approach to optimize antithrombotic strategies by identifying genetic variants that influence drug metabolism, pharmacodynamics, and clinical outcomes. Incorporating genetic information could refine therapy selection and dosing, especially for vitamin K antagonists (VKAs) and select direct oral anticoagulants (DOACs). Methods and Results: This review synthesizes evidence from clinical trials and observational studies evaluating the role of pharmacogenomic profiling in guiding antithrombotic therapy for AF. Key gene-drug interactions include CYP2C9 and VKORC1 polymorphisms affecting warfarin metabolism and sensitivity, as well as ABCB1 and CES1 variants influencing DOAC pharmacokinetics. Genotype-guided dosing algorithms have demonstrated improved time in therapeutic range (TTR), reduced bleeding events, and faster attainment of target INR in warfarin users. While routine pharmacogenomic testing has not yet been broadly adopted for DOACs, emerging data suggest associations between genetic variants and drug exposure levels, particularly in patients with renal impairment or polypharmacy. Clinical decision support tools integrating pharmacogenomic data are under development and may facilitate real-time implementation. Conclusion: Pharmacogenomic profiling enhances the personalization of antithrombotic therapy in atrial fibrillation by improving safety and therapeutic precision. As evidence matures and testing becomes more accessible, integration of genetic information into clinical workflows may become a standard component of AF management, aligning with the broader goals of precision cardiovascular care.