Pharmacogenetics of warfarin dosing in patients of African and European ancestry

Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictor...

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Bibliographic Details
Published in:Pharmacogenomics 2018-11, Vol.19 (17), p.1357-1371
Main Authors: Shendre, Aditi, Dillon, Chrisly, Limdi, Nita A
Format: Article
Language:English
Subjects:
Algorithms
Anticoagulants
Anticoagulants - administration & dosage
Black People - genetics
Bone surgery
Cardiac arrhythmia
Clinical trials
Consortia
Discordance
Dosage
Dose-Response Relationship, Drug
Drug dosages
Enzymes
Genes
Genomes
Genotype
Humans
Metabolism
Patients
pharmacogenetic dosing algorithms
Pharmacogenetics
Pharmacogenetics - methods
Polymorphism, Single Nucleotide - genetics
Prostheses
race
Review
Single-nucleotide polymorphism
Studies
Thromboembolism
Warfarin
Warfarin - administration & dosage
White People - genetics
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Summary:Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in and on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.
ISSN:1462-2416
1744-8042
1744-8042
DOI:10.2217/pgs-2018-0146