Abstract

ObjectiveTo study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement.MethodsWe searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms.ResultsA total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88–4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges.ConclusionsAll of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Highlights

  • Warfarin is one of the most widely prescribed anticoagulants for the prevention of thromboembolic events associated with atrial fibrillation, venous and arterial thrombosis, especially in patients of rheumatic heart disease with mechanic heart valve replacement

  • Since the discovery of the relationship between the gene polymorphisms of VKORC1 and CYP2C9 and the individual variability in warfarin dose requirements in the anticoagulation therapy [5,6,7,8], a number of pharmacogenetics-based algorithms integrating demographic data and different genotypes have been established to predict the dose of warfarin in Han-Chinese population [9,10,11,12,13,14,15,16] and other populations [17,18,19,20,21] all over the world

  • We aimed to evaluate the performance of pharmacogenetics-based warfarin dosing algorithms built in Han-Chinese population and two authoritative algorithms, namely International Warfarin Pharmacogenetics Consortium (IWPC) algorithm [17] and the Gage et al algorithm [18], in the initial and the stable warfarin treatment stages in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement

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Summary

Introduction

Warfarin is one of the most widely prescribed anticoagulants for the prevention of thromboembolic events associated with atrial fibrillation, venous and arterial thrombosis, especially in patients of rheumatic heart disease with mechanic heart valve replacement. Since the discovery of the relationship between the gene polymorphisms of VKORC1 and CYP2C9 and the individual variability in warfarin dose requirements in the anticoagulation therapy [5,6,7,8], a number of pharmacogenetics-based algorithms integrating demographic data and different genotypes have been established to predict the dose of warfarin in Han-Chinese population [9,10,11,12,13,14,15,16] and other populations [17,18,19,20,21] all over the world. The pharmacogenetics-based warfarin dosing algorithms established by other diseases might not be appropriate for predicting the warfarin dose in patients with mechanic heart valve replacement

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