Comparison of Maintenance Dose Predictions by Warfarin Dosing Algorithms Based on Chinese and Western Patients

Abstract Warfarin has a long record of safe and effective clinical use, and it remains one of the most commonly prescribed drugs for the prevention and treatment of thromboembolic conditions even in the era of direct oral anticoagulants. To address its large interindividual variability and narrow therapeutic window, the Clinical Pharmacogenetics Implementation Consortium has recommended using pharmacogenetic dosing algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al, to dose warfarin when genotype information is available. In China, dosing algorithms based on local patient populations have been developed and evaluated for predictive accuracy of warfarin maintenance doses. In this study, percentage deviations of doses predicted by 15 Chinese dosing algorithms from that by IWPC and Gage algorithms were systematically evaluated to understand the differences between Chinese and Western algorithms. In general, dose predictions by Chinese dosing algorithms tended to be lower than those predicted by IWPC or Gage algorithms for the most prevalent VKORC1 and CYP2C9 genotypes in the Chinese population. The extent of negative prediction deviation appeared to be largest in the younger age group with smaller body weight. Our findings are consistent with previous reports that Asians have a higher sensitivity to warfarin and require lower doses than Western populations.