A retrospective cohort study of pharmacogenetics of warfarin dosing in Chinese Adults with nonvalvular atrial fibrillation

Abstract

Background: The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fbrillation (NVAF) is still lacking. Aim: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. Method: The patients of this study were assigned to two cohorts to receive their dose of warfarin determined by a genetic and clinical factor (gene group) or dosing determined empirically(control group).We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR measurement during follow up. Secondary safety outcome included bleeding and thrombotic events. Results: Compared with the control group, the average TTR of the gene group was higher(68.4 ± 20.6) % vs (48.5 ± 21.6) %, P<0.001) .The frequency of the average INR monitoring times of the gene group was lower(P=0.02).At the end of follow-up, the gene group had a significant lower risk of cumulative incidences of ischemic stroke events in the adjusted model [relative risk (RR) 0.4 (95% CI 0.2 to 0.8),P =0.008] than control group. Conclusion: Genotype-guided warfarin administration increases the average TTR, reach higher TTR levels in the early anticoagulant phase and significantly reduce the risk of ischemic stroke events.