Evaluation of pharmacogenetic algorithms in dose prediction under low dose warfarin anticoagulation in mechanical cardiac valve replacement patients

CUI Li; LIU Jun

doi:10.3969/j.issn.1006-0111.2016.03.012

Message Board

Respected readers, authors and reviewers, you can add comments to this page on any questions about the contribution, review, editing and publication of this journal. We will give you an answer as soon as possible. Thank you for your support!

Name

E-mail

Phone

Title

Content

Verification Code

Objective Our aim is to assess the performance of warfarin pharmacogenetic algorithms in patients post mechanical cardiac valve replacement under low dose warfarin anticoagulation. Methods Based on the specified standard, from January 2012 to October 2013, 107 patients of Yijishan Hospital of Wannan Medical College were enrolled in the study. The target international normalized ratio (INR) ranging from 1.6 to 2.5 post surgery of mechanical cardiac valve replacement were set under low dose warfarin anticoagulation. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RELP and sequencing technology, and their doses of warfarin were adjusted by the results of INR. The patients were stratified into 3 groups according to the dose range:lower dose group (≤1.5 mg/d), intermediate dose group (1.5~4.5 mg/d) and higher dose group (≥4.5 mg/d). Then the predictive warfarin doses were calculated by international warfarin pharmaeogenetics consortium (IWPC) algorithm, the performance of the algorithm was evaluated by the mean absolute error (MAE) between warfarin predicted doses and actual stable doses, and the percentage of patients whose predicted doses within ideal doses (20% of their actual stable doses), over doses and under doses were compared. As well, the predicted warfarin doses were also regressed on stable doses, from which we obtain R² values. Results MAE between warfarin predicted doses and stable doses was (0.89±0.62) mg/d with R²=0.325. The percentage of warfarin predicted doses within ideal doses was 42.06%, and the percentage within ideal doses in higher group was 50.00%, which was higher than in intermediate dose group (43.75%) and lower dose group (11.11%). Conclusion The performance of IWPC algorithm used in warfarin anticoagulation dose assessment in Chinese Han population is infinite, the pharmacogenetic algorithms suitable for the Chinese Han population with low dose warfarin anticoagulation need to be further studied and verified clinically.

Evaluation of pharmacogenetic algorithms in dose prediction under low dose warfarin anticoagulation in mechanical cardiac valve replacement patients

1. Department of Pharmacy, Nanjing Red Cross Hospital, Nanjing 210001, China

2. Department of Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China

Received Date: 2014-11-17

Rev Recd Date: 2015-04-24

Key words:

Abstract: Objective Our aim is to assess the performance of warfarin pharmacogenetic algorithms in patients post mechanical cardiac valve replacement under low dose warfarin anticoagulation. Methods Based on the specified standard, from January 2012 to October 2013, 107 patients of Yijishan Hospital of Wannan Medical College were enrolled in the study. The target international normalized ratio (INR) ranging from 1.6 to 2.5 post surgery of mechanical cardiac valve replacement were set under low dose warfarin anticoagulation. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RELP and sequencing technology, and their doses of warfarin were adjusted by the results of INR. The patients were stratified into 3 groups according to the dose range:lower dose group (≤1.5 mg/d), intermediate dose group (1.5~4.5 mg/d) and higher dose group (≥4.5 mg/d). Then the predictive warfarin doses were calculated by international warfarin pharmaeogenetics consortium (IWPC) algorithm, the performance of the algorithm was evaluated by the mean absolute error (MAE) between warfarin predicted doses and actual stable doses, and the percentage of patients whose predicted doses within ideal doses (20% of their actual stable doses), over doses and under doses were compared. As well, the predicted warfarin doses were also regressed on stable doses, from which we obtain R² values. Results MAE between warfarin predicted doses and stable doses was (0.89±0.62) mg/d with R²=0.325. The percentage of warfarin predicted doses within ideal doses was 42.06%, and the percentage within ideal doses in higher group was 50.00%, which was higher than in intermediate dose group (43.75%) and lower dose group (11.11%). Conclusion The performance of IWPC algorithm used in warfarin anticoagulation dose assessment in Chinese Han population is infinite, the pharmacogenetic algorithms suitable for the Chinese Han population with low dose warfarin anticoagulation need to be further studied and verified clinically.

HTML

Reference (14)

[1]	Emery RW,Emery AM,Raikar GV,et al. Anticoagulation for mechanical heart valves:a role for patient based therapy[J]. J Thromb Thrombolysis,2008,25(1):18-25.
[2]	马风香,武金花,陈培恒.心脏瓣膜置换术后抗凝治疗的健康教育[J].中国医药导报,2009,6(18):158.
[3]	王兆钺.抗凝治疗及出血危险的研究现状[J].血栓与止血学,2011,17(5):231-233.
[4]	张魁,董然.中国人群瓣膜置换术后华法林个体化治疗最新研究进展[J].心肺血管病杂志,2012,3(2):217-219.
[5]	Klein TE,Altman RB,Eriksson N,et al. Estimation of the warfarin dose with clinical and pharmaeogenetic data[J].N Engl J Med,2009,360(8):753-764.
[6]	余靓平,宋洪涛,曾志勇,等.基于药物基因组学的华法林给药模型的验证[J].中华心血管病杂志,2012,40(7):614-619.
[7]	王红娟,刘瑜,杨洁,等.药物基因组学方程对中国患者低强度华法林抗凝治疗剂量的预测效果分析[J].中华老年多器官疾病杂志,2012,11(8):584-587.
[8]	郑红艳,宋杰.CYP2C9和VKORC1基因多态性对华法林剂量的影响[J].医学综述,2011,17(2):178-180.
[9]	Yang L,Ge W,Yu F,et al. Impact of VKORC1 gene polymorphism on inter-individual and interethnic warfarin dosage requirement-a systematic review and meta analysis[J].Thromb Res,2010,125(4):e159-e166.
[10]	谭胜蓝,彭娟,周新民,等.验证并比较华法林稳定剂量预测模型对中国心脏瓣膜置换术后患者预测准确性[J].中国临床药理学与治疗学杂志,2012,17(9):1026-1033.
[11]	王红娟,刘瑜,杨洁,等.中国患者华法林抗凝治疗剂量的药物基因组学相关性及药物基因组学方程的比较分析[J]. 中华老年多器官疾病杂志,2012,11(7):522-526.
[12]	Tang GM,Wu E,Lam YY,et al. Role of warfarin pharmacogenetic testing in clinical practice[J].Pharmacogenomics,2010,11(3):439-448.
[13]	Cen HJ,Zeng WT,Leng XY,et al. CYP4F2 rs2108622:a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement[J].Br J Clin Pharmacol,2010,70(2):234-240.
[14]	祝锦,张微,张伟娟,等.中国汉族人群华法林药物基因组学剂量预测公式比较[J].中国药学杂志,2011,46(24):1929-1934.

Message Board

Evaluation of pharmacogenetic algorithms in dose prediction under low dose warfarin anticoagulation in mechanical cardiac valve replacement patients

doi: 10.3969/j.issn.1006-0111.2016.03.012

Abstract

References

Proportional views

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Related

Proportional views