Pharmacogenetics of warfarin dosing in ChineseAdults with nonvalvular atrial fibrillation

Background: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. Methods - All patients with nonvalvular AF were randomly divided into two groups, genetic group and control group. We included genotypes for CYP2C9 and VKORC1 in the gene group，then doctors and pharmacists used the warfarin dosing algorithm and clinical information to determine patients’ initial dose, while in control group doses were determined by experince. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcome measure was the percentage of time in the therapeutic range (%TTR) of the INR during follow up after initiation of warfarin treatment. Results The average TTR was (68.36 ± 20.57) % vs (48.52 ± 21.56) %, P<0.001) in the gene group compared with the control group. At the end of follow-up, the genetic group had a significant lower risk of cumulative incidences of ischemic stroke events in the adjusted model [relative risk (RR) 0.38 (95% CI 0.18 to 0.80), log-rank test P =0.008] than control group. There was no significant difference in the risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding and intracerebral bleeding events between the two groups(P>0.05). Conclusion Genotype-guided dosing could improve the average TTR, improve the safety of treatment, achieve a higher level of TTR in the early anticoagulation period and reduce the risk of ischemic stroke events significantly.