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Thromb Haemost 2012; 108(06): 1132-1140
DOI: 10.1160/TH12-05-0362
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Estimation of the warfarin dose with a pharmacogenetic refinement algorithm in Chinese patients mainly under low-intensity warfarin anticoagulation

Qiang Xu   *
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Bin Xu   *
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Yuxiao Zhang   *
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Jie Yang
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Lei Gao
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Yan Zhang
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Hongjuan Wang
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Caiyi Lu
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Yusheng Zhao
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
,
Tong Yin
1   Institute of Geriatric Cardiology, General Hospital of People’s Liberation Army, Beijing, China
› Author Affiliations Financial support:This work was supported by grants from the National Natural Science Foundation of China (No. 30971259), and the Scientific and Technological Innovation Fund for Young Investigation, General Hospital of Chinese People’s Liberation Army (No. 09KMM23).
Further Information

Publication History

Received: 30 May 2012

Accepted after major revision: 14 August 2012

Publication Date:
30 November 2017 (online)

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Summary

Pharmacogenetic (PG) dosing algorithms have been confirmed to predict warfarin therapeutic dose more accurately;however, most of them are based on standard intensity of warfarin anticoagulation, and their utility outside this range is limited. This study was designed to develop and validate a PG refinement algorithm in Chinese patients mainly under low-intensity warfarin anticoagulation. Consented Chinese-Han patients (n=310) under stable warfarin treatment were randomly divided into a derivation (n=207) and a validation cohort (n=103), with 83% and 80% of the patients under low-intensity anticoagulation, respectively. In the derivation cohort, a PG algorithm was constructed on the basis of genotypes (CYP2C9*3 and VKORC1–1639A/G) and clinical data. After integrating additional covariates of international normalised ratio (INR) values (INR on day 4 of therapy and target INR) and genotype of CYP4F2 (rs2108622), a PG refinement algorithm was established and explained 54% of warfarin dose variability. In the validation cohort, warfarin dose prediction was more accurate (p <0.01) with the PG refinement algorithm than with the PG algorithm and the fixed dose approach (3 mg/day). In the entire cohort, the PG refinement algorithm could accurately identify larger proportions of patients with lower dose requirement (≤2 mg/day) and higher dose requirement (≥4 mg/day) than did the PG algorithm. In conclusion, PG refinement algorithm integrating early INR response and three genotypes CYP2C9*3, VKORC1–1639A/G, CYP4F2 rs2108622) improves the accuracy of warfarin dose prediction in Chinese patients mainly under low-intensity anticoagulation.

Keywords

Warfarin - pharmacogenetics - dosing algorithm - low-intensity anticoagulation

* These authors contributed equally


 

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