Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation
Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation
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DOI：
10.1161/circulationaha.107.737312
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发表时间：
2007-11-27
期刊：
影响因子：
37.8
通讯作者：
Carlquist, John F.
中科院分区：
文献类型：
--
作者：
Anderson, Jeffrey L.;Horne, Benjamin D.;Carlquist, John F.
背景 - 药物遗传学指导的华法林剂量是“个性化医疗”的一种有前景的应用，但尚未在随机试验中得到充分测试。方法和结果 - 同意开始服用华法林的患者 (n = 206) 被随机分配到药物遗传学指导或标准剂量。通过快速检测对口腔拭子 DNA 进行 CYP2C9 *2 和 CYP2C9 *3 以及 VKORC1 C1173T 基因分型。标准剂量遵循经验方案，而药物遗传学指导剂量遵循回归方程，包括 3 种遗传变异以及年龄、性别和体重。在第 0、3、5、8、21、60 和 90 天常规测量凝血酶原时间国际标准化比值 (INR)。研究药剂师对治疗策略不设盲，负责管理剂量调整。对患者进行长达 3 个月的随访。药物遗传学指导的预测剂量更准确地近似稳定剂量（P
Background-Pharmacogenetic-guided dosing of warfarin is a promising application of "personalized medicine" but has not been adequately tested in randomized trials.Methods and Results-Consenting patients (n=206) being initiated on warfarin were randomized to pharmacogenetic-guided or standard dosing. Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1 C1173T with a rapid assay. Standard dosing followed an empirical protocol, whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age, sex, and weight. Prothrombin time international normalized ratio (INR) was measured routinely on days 0, 3, 5, 8, 21, 60, and 90. A research pharmacist unblinded to treatment strategy managed dose adjustments. Patients were followed up for up to 3 months. Pharmacogenetic-guided predicted doses more accurately approximated stable doses ( P