Pharmacy Specialty Resident-Cardiology, UMass Memorial Medical Center, Worcester, MA, USA.
J Thromb Thrombolysis. 2010 Aug;30(2):220-5. doi: 10.1007/s11239-010-0459-3.
The objectives of this retrospective cohort study are to evaluate the accuracy of pharmacogenetic warfarin dosing algorithms in predicting therapeutic dose and to determine if this degree of accuracy warrants the routine use of genotyping to prospectively dose patients newly started on warfarin. Seventy-one patients of an outpatient anticoagulation clinic at an academic medical center who were age 18 years or older on a stable, therapeutic warfarin dose with international normalized ratio (INR) goal between 2.0 and 3.0, and cytochrome P450 isoenzyme 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genotypes available between January 1, 2007 and September 30, 2008 were included. Six pharmacogenetic warfarin dosing algorithms were identified from the medical literature. Additionally, a 5 mg fixed dose approach was evaluated. Three algorithms, Zhu et al. (Clin Chem 53:1199-1205, 2007), Gage et al. (J Clin Ther 84:326-331, 2008), and International Warfarin Pharmacogenetic Consortium (IWPC) (N Engl J Med 360:753-764, 2009) were similar in the primary accuracy endpoints with mean absolute error (MAE) ranging from 1.7 to 1.8 mg/day and coefficient of determination R (2) from 0.61 to 0.66. However, the Zhu et al. algorithm severely over-predicted dose (defined as >or=2x or >or=2 mg/day more than actual dose) in twice as many (14 vs. 7%) patients as Gage et al. 2008 and IWPC 2009. In conclusion, the algorithms published by Gage et al. 2008 and the IWPC 2009 were the two most accurate pharmacogenetically based equations available in the medical literature in predicting therapeutic warfarin dose in our study population. However, the degree of accuracy demonstrated does not support the routine use of genotyping to prospectively dose all patients newly started on warfarin.
本回顾性队列研究的目的是评估药物遗传学华法林剂量算法预测治疗剂量的准确性，并确定这种准确性是否足以支持常规使用基因分型来预测新开始使用华法林的患者的剂量。该研究纳入了一家学术医疗中心的门诊抗凝诊所的 71 名患者，这些患者年龄在 18 岁或以上，正在接受稳定的、治疗剂量的华法林治疗，国际标准化比值（INR）目标在 2.0 到 3.0 之间，并且可获得细胞色素 P450 同工酶 2C9（CYP2C9）和维生素 K 环氧化物还原酶复合物亚基 1（VKORC1）基因型。研究从医学文献中确定了 6 种药物遗传学华法林剂量算法。此外，还评估了 5 毫克固定剂量方法。Zhu 等人的 3 种算法（Clin Chem 53:1199-1205, 2007）、Gage 等人的算法（J Clin Ther 84:326-331, 2008）和国际华法林药物遗传学联合会（IWPC）的算法（N Engl J Med 360:753-764, 2009）在主要准确性终点上相似，平均绝对误差（MAE）范围为 1.7 到 1.8 毫克/天，决定系数 R（2）范围为 0.61 到 0.66。然而，Zhu 等人的算法严重高估了剂量（定义为比实际剂量多 >or=2x 或 >or=2 毫克/天），在两倍（14%比 7%）的患者中出现这种情况，而 Gage 等人的算法和 IWPC 2009 的算法则没有。总之，Gage 等人的算法和 IWPC 2009 是我们研究人群中预测治疗剂量的最准确的两种药物遗传学基础方程。然而，所表现出的准确性程度不支持常规使用基因分型来预测所有新开始使用华法林的患者的剂量。
