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Pharmacogenetic warfarin dosing shows marginal to no benefit
The inter-individual variation in warfarin dosing requirements and narrow therapeutic index for anticoagulation necessitates a personalized dosing regimen. Variation in dosing requirements are in part explained by genetic polymorphism in CYP (involved in warfarin metabolism) and VKOR (a warfarin target) genes. A dosing strategy informed by these polymorphism may hold promise to improve anticoagulation control. In three large randomized trials of similar design, a sophisticated pharmacogenetic approach to warfarin initiation was compared with standard care. All three studies used the percentage of time in therapeutic range as the primary end-point. None of the studies were powered to assess bleeding complications. A genotype-guided dosing approach failed to demonstrate improvements in anticoagulation control for the two largest studies. In the …
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