• Jin Li, Tao Chen, Fangfang Jie, Haiyan Xiang, Li Huang, Hongfa Jiang, Fei Lu, Shuqiang Zhu, Lidong Wu, and Yanhua Tang.
• Emergency Department of the Second Affiliated Hospital of Nanchang University, Nanchang, China.
• Medicine (Baltimore). 2022 Jul 22; 101 (29): e29626e29626.

BackgroundWarfarin is the most recommended oral anticoagulant after artificial mechanical valve replacement therapy. However, the narrow therapeutic window and varying safety and efficacy in individuals make dose determination difficult. It may cause adverse events such as hemorrhage or thromboembolism. Therefore, advanced algorithms are urgently required for the use of warfarin.ObjectiveTo establish a warfarin dose model for patients after prosthetic mechanical valve replacement in southern China in combination with clinical and genetic variables, and to improve the accuracy and ideal prediction percentage of the model.MethodsClinical data of 476 patients were tracked and recorded in detail. The gene polymorphisms of VKORC1 (rs9923231, rs9934438, rs7196161, and rs7294), CYP2C9 (rs1057910), CYP1A2 (rs2069514), GGCX (rs699664), and UGT1A1 (rs887829) were determined using Sanger sequencing. Multiple linear regressions were used to analyze the gene polymorphisms and the contribution of clinical data variables; the variables that caused multicollinearity were screened stepwise and excluded to establish an algorithm model for predicting the daily maintenance dose of warfarin. The ideal predicted percentage was used to test clinical effectiveness.ResultsA total of 395 patients were included. Univariate linear regression analysis suggested that CYP1A2 (rs2069514) and UGT1A1 (rs887829) were not associated with the daily maintenance dose of warfarin. The new algorithm model established based on multiple linear regression was as follows: Y = 1.081 - 0.011 (age) + 1.532 (body surface area)-0.807 (rs9923231 AA) + 1.788 (rs9923231 GG) + 0.530 (rs1057910 AA)-1.061 (rs1057910 AG)-0.321 (rs699664 AA). The model accounted for 61.7% of individualized medication differences, with an ideal prediction percentage of 69%.ConclusionGGCX (rs699664) may be a potential predictor of warfarin dose, and our newly established model is expected to guide the individualized use of warfarin in clinical practice in southern China.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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