Validation of Warfarin Pharmacogenetic Algorithms In 586 Han Chinese Patients

Pan, Qi; Huang, Shujun; Chen, Xiaoying; Yuan, Yayan; Yu, Yajun; Tao, Liang; Zhang, Zhenlu; Xu, Mousheng

doi:10.2217/pgs.15.87

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…Two possible explanations for this observation are that the sample size for derivation of IWPC ( N = 4043) and Gage et al ( N = 1015) algorithms is much larger than the two Thai algorithms, resulting in more data on relationship between genetic and nongenetic factors and warfarin dose‐response captured by the algorithms; second, more nongenetic factors clinically affecting warfarin dose requirement, such as height or BSA, were incorporated in the IWPC and Gage et al algorithms, but not in Sangviroon et al and Sarapakdi et al algorithms. However, this favorable performance of IWPC and Gage et al algorithms is inconsistent with several validation studies in East Asian population, such as Han Chinese, Japanese, or Korean that found these 2 algorithms were inferior to algorithms derived from specific ethnic group . Furthermore, performance of several ethnic‐specific algorithms in our study, particularly Cho et al, Miao et al, and Huang et al algorithms, but Ohno et al or the two Thai algorithms, was inferior to IWPC and Gage et al algorithms.…”

Section: Discussioncontrasting

confidence: 99%

Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Chumnumwat

Kong

Lucksiri

et al. 2018

Cardiovascular Therapeutics

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Section: Discussioncontrasting

confidence: 99%

Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Chumnumwat

Kong

Lucksiri

et al. 2018

Cardiovascular Therapeutics

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“…Several previous studies have also found that warfarin dosing algorithms perform poorly in patients requiring higher doses. Peng et al . compared the stable maintenance dose of 586 Chinese patients against maintenance doses predicted using nine algorithms.…”

Section: Discussionmentioning

confidence: 99%

“…There were six patients requiring doses ≥7 mg/day in their study. Peng et al . found that the proportion of underpredicted doses in each of the algorithms were more than 80%.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta‐analysis

Saffian

Duffull

Wright

2017

Clin Pharma and Therapeutics

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There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I = 24%).

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“…The most classic pharmacogenetic warfarin dosing algorithm was the International Warfarin Pharmacogenetics Consortium (IWPC) algorithm, which substituted 5,000 patients from 4 continents into pharmacogenetic algorithm and could explain 46% interindividual variability ( Johnson, 2012 ). But some studies have proved that IWPC algorithm was not suitable for the Han-Chinese ( Peng et al., 2015 ). To our knowledge, few studies have been published on the pharmacogenetic-guided warfarin dosing algorithms in the elder Han-Chinese population so far.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic-Guided Algorithm to Improve Daily Dose of Warfarin in Elder Han-Chinese Population

et al. 2020

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Objectives: To verify the accuracy of the International Warfarin Pharmacogenetics Consortium (IWPC) algorithm, identify the effects of genetic and clinical factors on warfarin stable dose, and to establish a new warfarin stable dose prediction algorithm for the elderly Han-Chinese population under the guidance of pharmacogenetics. Methods: According to the inclusion criteria, 544 non-valvular atrial fibrillation patients taking warfarin for anticoagulation treatment were enrolled. Data information of three groups including the whole population, people under 65 years old and over 65 years old were substituted into the IWPC algorithm respectively to verify its accuracy. The basic data and clinical information of 360 elderly people were collected for statistical analysis and the genotypes of VKORC1-G1639A and CYP2C9 were detected by Sanger sequencing. The new algorithm of the elder pharmacogenetics warfarin dosing was obtained by stepwise multiple regression. The determination coefficient (R2), root mean squared error (RMSE), and the proportion of the predicted value within the true value range of ±20%(20%-p) were used to evaluate the accuracy of the IWPC algorithm and the new algorithm. Results: Among the three different age groups, the warfarin stable dose predictive accuracy of IWPC algorithm was the lowest in the elderly patients above 65-year-old. In this study, the important factors influencing the stable dose of warfarin in the elderly Han-Chinese were height, weight, body surface area, serum creatinine level, amiodarone usage, CYP2C9 (*1*2, *1*3), and VKORC1 (GG/GA) genotypes. By means of stepwise multiple regression analysis, we established a new elder warfarin dosing algorithm (R 2 =0.3714) containing height, creatinine, amiodarone usage, CYP2C9 (*1*2 or *1*3), and VKORC1 (GA or GG) genotypes. The prediction accuracy and clinical availability of the Elderly algorithm was significantly better than that of IWPC algorithm verified by RMSE, R2, and (20%-p) methods.

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Validation of Warfarin Pharmacogenetic Algorithms In 586 Han Chinese Patients

Abstract: Algorithms built for specific ethnic groups and preassigned-dose groups are suggested for better prediction.

Cited by 14 publications

References 28 publications

Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Comparative performance of pharmacogenetics‐based warfarin dosing algorithms derived from Caucasian, Asian, and mixed races in Thai population

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta‐analysis

Pharmacogenetic-Guided Algorithm to Improve Daily Dose of Warfarin in Elder Han-Chinese Population

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