Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Anzhen Road #2, Beijing, 100029, China.
BMC Cardiovasc Disord. 2022 Apr 19;22(1):183. doi: 10.1186/s12872-022-02620-x.
To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement.
A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group (n = 86) and an experimental (n = 86) group based on acceptance of genetic testing. In the experimental group, three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique, and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U.S. Food and Drug Administration (FDA). In the control group, warfarin (3 mg per night) was used as the initial dose. The international normalized ratio (INR) of each patient was continuously monitored after medication. The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored, and the incidence of various adverse events was compared between the groups.
Based on the results of genetic testing, 68 patients received 3-4 mg/d (79.1%), 10 patients received 0.5-2 mg/d (11.6%), and eight patients received 5-7 mg/d (9.3%) as the initial dosages of warfarin in the experimental group. The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3% and 73.3%, respectively, in the experimental group, and 29.8% and 58.3%, respectively, in the control group. The INR critical values during hospitalization occurred in 2.3% in the experimental group and in 7.1% in the control group, while the percentage of the patients meeting the target INR after 3 months was 86.1% in the experimental group and 83.1% in the control group.
Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.
探讨 VKORC1 和 CYP2C9 基因检测在主动脉瓣置换术后华法林剂量确定中的作用。
根据是否接受基因检测，将 172 例主动脉瓣置换术后接受华法林治疗的患者分为对照组（n=86）和实验组（n=86）。实验组采用聚合酶链反应-限制性片段长度多态性技术检测 VKORC1 和 CYP2C9 三个基因座，根据基因检测结果和美国食品药品监督管理局（FDA）推荐的华法林口服剂量表确定初始剂量。对照组采用华法林（每晚 3mg）作为初始剂量。两组患者服药后均连续监测国际标准化比值（INR）。监测两组患者在特定时间点及出院后 3 个月时达到目标 INR 的比例，比较两组患者不良反应的发生率。
根据基因检测结果，实验组患者华法林初始剂量为 3-4mg/d 者 68 例（79.1%），0.5-2mg/d 者 10 例（11.6%），5-7mg/d 者 8 例（9.3%）。实验组患者术后第 3、6 天达到目标 INR 的比例分别为 45.3%和 73.3%，对照组分别为 29.8%和 58.3%。实验组患者住院期间 INR 危急值发生率为 2.3%，对照组为 7.1%，出院后 3 个月达到目标 INR 的比例实验组为 86.1%，对照组为 83.1%。
基因检测可指导心脏瓣膜置换术后华法林初始剂量的选择，从而快速达到稳定剂量。
