title: [Companion Diagnostics for Thrombotic Disease].
abstract: In recent years, thrombotic disease, including myocardial infarction and ischemic stroke, has rapidly increased in Japan. To treat and prevent thromboembolism, warfarin has been commonly prescribed for a long period as an oral anticoagulant. However, it is difficult to define an appropriate warfarin dose because of large inter-individual variability in dose requirements and the narrow therapeutic range. Recent pharmacogenomic (PGx) studies have shown that several single nucleotide polymorphisms (SNPs) in CYP2C9 (warfarin metabolic enzyme) and VKORC1 (warfarin target enzyme) are responsible for an individual's warfarin sensitivity. In order to realize personalized warfarin treatment, algorithms to estimate the required warfarin dose based on PGx are under consideration, including the cost-effectiveness. Recently, novel oral anticoagulants (NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban) have become available as well as alternatives to warfarin treatment for the prevention of ischemic stroke in non-valvular atrial fibrillation. Although NOACs are prescribed at a fixed-dose without frequent monitoring of blood coagulability, it has been reported that there is inter-individual variability in the blood concentration of dabigatran caused by gene polymorphisms. Further studies are needed to perform more effective and safer anticoagulant therapy using NOACs. Progress in PGx studies and the realization of personalized anticoagulant therapy are expected in the future. [Review].
authors.forename: Yuya
authors.initials: Y
authors.lastname: Masuda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuno
authors.forename: Chikara
authors.initials: C
authors.lastname: Shimizu
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D000069604:Dabigatran / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D013927:Thrombosis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000069604:Dabigatran