Warfarin-dosing algorithm based on CYP2 C9 and VKORC1 genotypes, age and height of patients with atrial fibrillation

JIANG Nianxin; GE Junwei; XIAN Yuqiong; HUANG Shaoying; LI Yansong

doi:10.3969/j.issn.1002-266X.2016.11.005

Abstract：Objective To develop and evaluate the warfarin-dosing algorithm based on cytochrome P 4502 C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes, age and height of patients with atrial fibril-lation (AF).Methods A total of 122 AF patients were included and their genotypes of CYP2C9 (rs1057910) and VKORC1 (rs9923231) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Multiple linear regression was performed to develop a warfarin dosing algorithm which was based on age , height, CYP2C9 and VKORC1 genotypes of AF patients .Another 60 AF patients were enrolled and randomly assigned into the con-trol group (n=30) and experimental group (n=30) .The experimental group received warfarin of "predicted warfarin dose"based on warfarin dosing algorithm , and the control group received warfarin of 2.5 mg/d.Both groups received war-farin for 7 days and then were adjusted to INR until reaching the stable warfarin maintenance dose .The time to reach a sta-ble warfarin maintenance dose was compared between the control group and experimental group .Results The warfarin-do-sing=0.438-0.0143 ×age+0.0149 ×height-0.324 ×CYP2C9 ×3+0.209 ×VKORC1, R2 =0.564.During the 50 day follow-up, there were 26 patients in the control group and 19 patients in the experimental group who acquired warfarin maintenance dose, with significant difference (P＜0.05).The mean time from initiation to warfarin maintenance dose was significantly shorted in the experimental group (25.8 ±1.7 d) than that in the control group (33.1 ±1.9 d), P＜0.05. Conclusion A new warfarin-dosing algorithm is developed based on CYP 2C9 and VKORC1 genotypes, age and height and it can shorten the time from initiation to warfarin maintenance dose in AF patients with warfarin therapy .