Genotype‐guided warfarin therapy: Still of only questionable value two decades on

摘要: WHAT IS KNOWN AND OBJECTIVE Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its implementation. The objective this critique is re-evaluate key pharmacogenetic with a view explaining why may be so. METHODS Major widely-cited as well recent meta-analyses were identified critical analysis these was undertaken identify factors that account for poor implementation pre-treatment genotyping. RESULTS DISCUSSION Critical examination major number methodological concerns such marked variations study designs different variously-defined measures outcome. Genotype testing involved only limited CYP2C9/VKORC1 alleles. Claims benefits genotyping are based almost exclusively on INR-related parameters which known highly time-labile value predicting risk or benefit. This evidenced by lack any significant effect rates bleeding thromboembolic events. Neither the effects potential phenoconversion medication non-adherence populations been adequately investigated. Although ethnicity/race now better characterised, power determine whether claimed indication-sensitive. NEW CONCLUSION Since 60% inter-individual variability dose/response due other (many non-genetic), expectations eliminating simply over-optimistic efforts cost-ineffective. Real-world not always corroborated trials-based claims It time consider redirecting scarce resources away from pharmacogenetics research potentially greater relevance.