Anticoagulation endpoints with clinical implementation of warfarin pharmacogenetic dosing in a real-world setting: A proposal for a new pharmacogenetic dosing approach.
Anticoagulation endpoints with clinical implementation of warfarin pharmacogenetic dosing in a real-world setting: A proposal for a new pharmacogenetic dosing approach.
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DOI：
10.1002/cpt.558
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发表时间：
2017-05
影响因子：
6.7
通讯作者：
Cavallari LH
中科院分区：
文献类型：
--
作者：
Arwood MJ;Deng J;Drozda K;Pugach O;Nutescu EA;Schmidt S;Duarte JD;Cavallari LH
使用华法林有效地实现治疗性抗凝对于降低血栓形成和出血风险很重要，并且受基因型影响。利用来自257例接受VKORC 1和CYP 2C 9基因型指导华法林给药的患者的数据，我们旨在检查抗凝终点的基因型相关差异，并推导出一种新的药物遗传学列线图，以更优化华法林剂量。我们观察到VKORC 1或CYP 2C 9等位基因功能降低分别为0、1或≥2的患者在达到治疗性国际标准化比值（INR）的时间上存在显著差异。（7.8±5.8、7.2±4.7和5.4±4.6天，P=0.0004）和前28天治疗范围内的平均时间百分比（22.2、27.8和32.2%，P=0.0127）。这些数据表明，对于具有0至1个VKORC 1/CYP 2C 9变体的患者，需要更积极的给药，以更有效地实现治疗性抗凝。在此，我们提供了一种新的动力学/药效学衍生的剂量诺模图优化异质性患者人群。
Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8±5.8, 7.2±4.7, and 5.4±4.6 days, P=0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P=0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic-derived dosing nomogram optimized for a heterogeneous patient population.