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

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (9): 1026-1033.

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

谭胜蓝¹, 彭娟¹, 周新民², 宋国宝², 刘立明², 张伟¹, 刘昭前¹, 周宏灏¹, 李智¹

¹中南大学临床药理研究所,长沙 410078, 湖南;
²中南大学湘雅二医院胸心外科,长沙 410011,湖南

收稿日期:2012-06-25 修回日期:2012-07-16 发布日期:2012-09-25
通讯作者: 李智,通信作者,男,副教授,主要从事遗传药理学和临床药理学研究。Tel: 0731-84805380 E-mail: lizhi489@163.com
作者简介:谭胜蓝,女,博士研究生,主要从事遗传药理学和临床药理学研究。Tel: 0731-84805380 E-mail: shenglantan@gmail.com.
基金资助:
国家高技术研究发展计划(863计划)(2012AA02A518); 湖南省高校创新平台开放基金(11K073)

Validation and comparison of warfarin stable dosage prediction algorithms in Chinese patients undergoing heart valve replacement

TAN Sheng-lan¹, PENG Juan¹, ZHOU Xin-min², SONG Guo-bao², LIU Li-ming², ZHANG Wei¹, LIU Zhao-qian¹, ZHOU Hong-hao¹, LI Zhi¹

¹Institute of Clinical Pharmacology, Central South University, Changsha 410078, Hunan, China;
²Department of Cardio-thoracic Surgery, the Second Xiangya Hospital of Central South University, Changsha 410011,Hunan, China

Received:2012-06-25 Revised:2012-07-16 Published:2012-09-25

摘要/Abstract

摘要： 目的验证并比较12个华法林稳定剂量预测模型及目前国内常用固定剂量给药方案(2.5 mg/d)对本院心脏瓣膜置换术后患者的预测准确性。方法收集已达华法林稳定剂量的804例人工心脏瓣膜置换术后患者完整临床资料,采集每位患者外周血 2 mL,焦磷酸测序法检测其VKORC1-1639G>A和CYP2C9^*3基因型。Pubmed检索出符合筛选条件的12个华法林稳定剂量预测模型。采用绝对误差均值(MAE)和预测百分比两个指标评价并比较各模型预测准确性。结果共有9个预测模型及固定剂量方案计算的MAE小于±1.0 mg/d,其中MAE最低的三个模型分别为Gage、Wen和Ohno。共有8个模型及固定剂量方案计算理想预测百分比大于40%,其中理想预测百分比最高的三个模型分别为Wen、Huang和Gage。敏感性分析表明预测模型对中剂量(稳定剂量>1.88,且<4.38 mg/d)和高剂量(稳定剂量≥4.38 mg/d)患者预测准确性较好,但对低剂量患者(稳定剂量≤1.88 mg/d)预测较差;固定剂量方案对高、低剂量患者预测准确性均为0。结论基因导向的华法林稳定剂量预测模型可以较好预测大部分患者,具有临床应用价值。

关键词: 华法林, 模型, VKORC1, CYP2C9

Abstract: AIM: To validate and compare 12 previously published warfarin stable dosage prediction algorithms and the fixed dosing regimen (2.5 mg/d) as applied to our patients undergoing heart valve replacement (HVR). METHODS: 804 Chinese HVR patients on stable maintenance dose of warfarin were enrolled from our hospital. Comprehensive clinical data were collected. 2 mL blood sample was drawn from each patient for VKORC1-1639G>A and CYP2C9^*3 genotype analyses by pyrosequencing method. 12 previously published algorithms were selected from Pubmed database for validation and comparison. The performance of all the algorithms was determined by mean absolute error (MAE) and percentage of ideal/under/over prediction.RESULTS: 9 algorithms and the fixed dosing method showed a MAE less than±1.0 mg/d, of which the Gage, Wen and Ohno algorithms had the lowest MAE. 8 algorithms and the fixed dosing regimen showed more than 40% of ideal prediction, of which the Wen, Huang and Gage algorithms showed the highest percentage of ideal prediction. Sensitivity analysis demonstrated that these algorithms had better prediction for the medium-dose (>1.88 and <4.38 mg/d) and high-dose (≥4.38 mg/d) patients but showed poor performance for the low-dose (≤1.88 mg/d) patients.The ideal prediction of the fixed dosing regimen for both low-dose and high-dose patients was 0.CONCLUSION: Genotype-guided warfarin dosage prediction algorithms could accurately predict most of our patients, therefore these algorithms may be potentially useful in clinical practice.

Key words: Warfarin, Algorithms, VKORC1, CYP2C9

中图分类号:

R969

谭胜蓝, 彭娟, 周新民, 宋国宝, 刘立明, 张伟, 刘昭前, 周宏灏, 李智. 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, 2012, 17(9): 1026-1033.

TAN Sheng-lan, PENG Juan, ZHOU Xin-min, SONG Guo-bao, LIU Li-ming, ZHANG Wei, LIU Zhao-qian, ZHOU Hong-hao, LI Zhi. Validation and comparison of warfarin stable dosage prediction algorithms in Chinese patients undergoing heart valve replacement[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(9): 1026-1033.

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