[Companion Diagnostics for Thrombotic Disease].

Area of Science:

• Pharmacogenomics
• Cardiovascular Medicine
• Drug Metabolism

Background:

• Increasing incidence of thrombotic diseases like myocardial infarction and ischemic stroke in Japan.
• Warfarin, a long-standing oral anticoagulant, presents challenges in dosing due to inter-individual variability and a narrow therapeutic range.
• Genetic variations in CYP2C9 and VKORC1 significantly influence warfarin sensitivity.

Purpose of the Study:

• To review the role of pharmacogenomics (PGx) in personalized warfarin therapy.
• To discuss the emergence and potential PGx implications of novel oral anticoagulants (NOACs).
• To highlight the need for further research in personalized anticoagulant strategies.

Main Methods:

• Review of recent pharmacogenomic studies on warfarin.
• Analysis of genetic polymorphisms affecting drug metabolism and target enzymes (CYP2C9, VKORC1).
• Examination of clinical data and research on NOACs (dabigatran, rivaroxaban, apixaban, edoxaban).

Main Results:

• Specific single nucleotide polymorphisms (SNPs) in CYP2C9 and VKORC1 explain a significant portion of warfarin dose variability.
• PGx-based algorithms are being developed for personalized warfarin dosing.
• While NOACs are fixed-dose, inter-individual variability in drug concentration, potentially due to gene polymorphisms (e.g., dabigatran), has been observed.

Conclusions:

• Pharmacogenomics is crucial for optimizing warfarin therapy and enabling personalized treatment.
• Further investigation into the pharmacogenomic aspects of NOACs is necessary for safer and more effective anticoagulant therapy.
• Advancements in PGx are expected to drive personalized anticoagulant strategies in the future.