心脏瓣膜置换术后华法林药物基因导向个体化抗凝治疗的临床意义

Clinical significance of individualized anticoagulant therapy with warfarin based on pharmacogenomics in patients after cardiac valve replacement

目的 探讨心脏瓣膜置换术后华法林药物基因导向个体化抗凝治疗的临床意义.方法 选取2015年5-9月于首都医科大学附属北京安贞医院心外科就诊需行心脏瓣膜置换术的患者60例,完全随机分为基因组和对照组,每组30例.基因组患者接受基因检测结果指导剂量华法林3d,对照组患者接受3 mg华法林3d,然后2组患者根据国际标准化比值（INR）调整华法林剂量.主要终点指标为INR值在1.8 -2.5的时间（达标时间）在2个月内所占的百分比.并比较2组达标时间百分比、抗凝不足时间百分比、过度抗凝时间百分比差异.结果 共有56例患者完成随访,其中基因组27例、对照组29例.基因组INR达标时间百分比为（78±16）％,而对照组则为（59±17）％,差异有统计学意义（P＜0.001）.基因组抗凝达标时间中位数为27（14,28）d,对照组达标时间中位数为21（7,25）d,差异有统计学意义（P =0.003）;抗凝不足时间百分比、过度抗凝时间百分比、出血和栓塞事件发生率2组差异无统计学意义（P＞0.05）.结论 心脏瓣膜置换术后患者初始抗凝治疗时,华法林基因指导剂量优于标准剂量.

Objective To discuss the clinical significance of individualized anticoagulant therapy with warfarin based on pharmacogenomics in patients after cardiac valve replacement.Methods Totally 60 patients undergoing cardiac valve surgery from May to September 2015 were randomly divided into genome group and control group （30 cases in each group）.The warfarin doses were prescribed according to pharmacogenetic-based algorithms in genome group,while standard doses of warfarin were given in control group on the first 3 days;then the doses were adjusted according to international normalized ratio （INR）.The primary outcome measure was the time percentage of reaching therapeutic INR 1.8 to 2.5 （standard anticoagucation） during the first 2 months.The time percentages of standard anticoagulation,inadequate anticoagulation and excessive anticoagulation were compared between groups.Results A total of 56 patients completed follow-up,including 27 cases in genotype group and 29 cases in control group.The time percentages of standard anticoagulation was （78 ± 16） % in genome group and （59 ± 17） % in control group,with significant difference between groups （P 〈 0.001）.The median time of reaching therapeutic INR was 27 （14,28） days in genome group and 21 （7,25） days in control group,with significant difference between groups （P =0.003）.There were no significant differences in time percentage of inadequate anticoagulation and excessive anticoagulation between groups （P 〉 0.05）.Conclusion Parmacogenetic-based dosing is better than standard dosing during the initiation of warfarin therapy in patients with heart value replacement.