A prediction study of warfarin individual stable dose after mechanical heart valve replacement: adaptive neural-fuzzy inference system prediction

Huan Tao, Qian Li, Qin Zhou, Jie Chen, Bo Fu, Jing Wang, Wenzhe Qin, Jianglong Hou, Jin Chen, Li Dong, on behalf of the CLIATHVR multicenter clinical study team

It's difficult but urgent to achieve the individualized rational medication of the warfarin, we aim to predict the individualized warfarin stable dose though the artificial intelligent Adaptive neural-fuzzy inference system (ANFIS). Our retrospective analysis based on a clinical database, involving 21,863 patients from 15 Chinese provinces who receive oral warfarin after the heart valve replacement. They were allocated into four groups: the external validation group (A group), the internal validation group (B group), training group (C group) and stratified training group (D group). We used a univariate analysis of general linear models(GLM-univariate) to select the input variables and construct two prediction models by the ANFIS with the training and stratified training group, and then verify models with two validation groups by the mean squared error(MSE), mean absolute error(MAE) and the ideal predicted percentage. A total of 13,639 eligible patients were selected, including 1639 in A group, 3000 in B group, 9000 in C group, and 3192 in D group. Nine input variables were selected out and two five-layered ANFIS models were built. ANFIS model achieved the highest total ideal predicted percentage 63.7%. In the dose subgroups, all the models performed best in the intermediate-dose group with the ideal predicted percentage 82.4~ 86.4%, and the use of the stratified training group slightly increased the prediction accuracy in low-dose group by 8.8 and 5.2%, respectively. As a preliminary attempt, ANFIS model predicted the warfarin stable dose properly after heart valve surgery among Chinese, and also proved that Chinese need lower anticoagulation intensity INR (1.5-2.5) to warfarin by reference to the recommended INR (2.5-3.5) in the developed countries.