National Medical Research Center of Cardiology of Ministry of Health of the Russian Federation, Moscow, Russian Federation.
DNA-Technology JSC, Moscow, Russian Federation.
Pharmacogenomics J. 2020 Oct;20(5):687-694. doi: 10.1038/s41397-020-0157-2. Epub 2020 Feb 6.
A total of 263 warfarin naive patients with indications to long-term anticoagulation were included in prospective multicenter study and randomized into Pharmacogenetics and Standard dosing groups. The loading warfarin dose in Pharmacogenetics group was calculated by Gage algorithm and corrected starting on day 5 of treatment according to INR. In Standard dosing group warfarin initial dose was 5 mg and starting on day 3 of treatment it was titrated according to INR. Pharmacogenetics dosing in comparison with prescription of starting dose of 5 mg decreased major bleedings (0 vs. 6, p = 0.031), time to target INR (11 [9-14] vs. 17 [15-24] days, p = 0.046), and frequency of INR fluctuations ≥4.0 (11% vs. 30.9%, p = 0.002). The advantages of the pharmacogenetics dosing were mainly achieved due to the patients with increased warfarin sensitivity.
共纳入 263 例华法林初治且具有长期抗凝指征的患者,前瞻性多中心研究并随机分为药物基因组学组和标准剂量组。药物基因组学组的负荷华法林剂量根据 Gage 算法计算,并根据 INR 于治疗第 5 天开始校正。标准剂量组的初始华法林剂量为 5mg,并于治疗第 3 天开始根据 INR 滴定。与起始剂量 5mg 的处方相比,药物基因组学剂量可降低大出血(0 与 6,p=0.031)、达到目标 INR 的时间(11[9-14]与 17[15-24]天,p=0.046)和 INR 波动≥4.0 的频率(11%与 30.9%,p=0.002)。药物基因组学剂量的优势主要归因于华法林敏感性增加的患者。