Methodological Analysis Of Warfarin Dose Prediction Without Gene And Study On Clinical Safety And Efficacy Of Pharmacist Participating In Warfarin Anticoagulant Therapy

Objective: To provide a method and tool for predicting the dose of warfarin without gene for patients in areas where warfarin related genotypes are detected unconditionally.Multiple linear regression(MLR)and Bayesian method are the main methods used in warfarin dose prediction.Warfarin Dosing which is established by Gage et al.and International Warfarin Pharmacogenetics Consortium(IWPC)Warfarin Dose Calculator are the main assistant tools for warfarin dose prediction based on MLR method.Warfarin Dose Calculator(WDC)is the assistant tool for warfarin dose prediction based on Bayesian method.The aim of this study is to evaluate the predictive performance of the above three warfarin dose prediction assistant tools based on multiple linear regression and Bayesian method in the absence of warfarin related genotypes,in order to provide help for patients using warfarin in areas where there is unconditional warfarin related genotypes detection.Besides,we conducted a Meta analysis on the impact of pharmacist led anticoagulant model on clinical outcomes compared with other anticoagulant models.】Method: The patients who met the inclusion and exclusion criteria of this study and took warfarin from September 2018 to October 2020 in our hospital were retrospectively collected by electronic medical record system.The above three warfarin dose prediction assistant tools were used to predict warfarin maintenance doses.The predicted performance of each tool was evaluated by calculating the mean prediction error(MPE),root mean square error(RMSE)and the percentage of patients whose prediction error was within ± 20% of the actual maintenance dose.The predictive accuracy of methods was compared by F test.Pearson’s correlation analysis was used to estimate the actual and predicted maintenance warfarin dose.We searched Pub Med,Embase,Cochrane Library conducted up to April 13,2020.Studies that compared the percentage of time within the target therapeutic range(TTR),the percentage of time within the expanded therapeutic range(TER),bleeding events,thrombosis events,and mortality during pharmacist managed anticoagulation model with other anticoagulation models.All statistical analyses were performed by SPSS statistics 26.0 and Stata 12.0 software,p < 0.05 was considered to have significant difference.Results: The mean prediction errors of Warfarin Dosing and IWPC warfarin dose calculator based on multiple linear regression were 1.32 mg / day(95% CI: 1.13-1.51)and 1.64 mg / day(95% CI: 1.44-1.84),respectively.The root mean square errors were1.58 mg / day and 1.87 mg / day.The percentage of patients whose prediction errors within ± 20% of the actual maintenance dose were 18.07% and 10.84%.The mean prediction errors of the prior and posteriori of the Bayesian Warfarin Dose Calculator were 0.36 mg / day(95% CI: 0.19-0.54)and 0.33 mg / day(95% CI: 0.24-0.43),respectively.The root mean square errors were 0.87 mg / day and 0.54 mg / day.The percentage of patients whose prediction errors were within ± 20% of the actual maintenance dose were 51.80% and 73.50%.Bayesian Posteriori had the best prediction performance,and the predictive accuracy of Bayesian Priori and Posteriori is significantly higher than that of Gage and IWPC(p < 0.05).A total of 23 studies,including 10 RCTs and 13 observational cohort studies with 10,772 patients were identified in the Meta analysis.Pharmacist managed anticoagulation model can significantly reduce total bleeding(p = 0.006),minor bleeding(p = 0.013)and thrombosis events(p = 0.002)compared with other models.However,no significant differences in TTR(p = 0.076),TER(p = 0.156),major bleeding events(p = 0.139)and mortality(p = 0.519)were found.In analysis conducted by intervention,the pharmacist group could significantly reduce total bleeding(p = 0.008),minor bleeding(p = 0.013)and thrombosis events(p = 0.001)compared with physician group.Conclusion: Among the three assistant tools for warfarin dose prediction,Warfarin Dose Calculator based on Bayesian method may be more suitable for warfarin dose prediction of patients in unconditional warfarin related genotypes detection area.Compared with other anticoagulation models,pharmacist managed anticoagulation model can significantly reduce the risk of total bleeding,minor bleeding and thrombosis events in anticoagulant patients.