华法林周剂量给药策略治疗非瓣膜性心房颤动患者的疗效及可行性分析

The Efficacy and Feasibility of Weekly-dosage Strategy of Warfarin Prescription in Patients With Non-valvular Atrial Fibrillation

目的:对于非瓣膜性心房颤动患者,评估两种不同华法林给药策略的抗凝疗效。方法:选择我院2015年1月至2019年1月收治的有抗凝指征、首次给药1周后国际标准化比值(INR)未达标的163例非瓣膜性心房颤动患者,随机分为周剂量组(n=82)和日剂量组(n=81)。周剂量组按每周总剂量调整华法林日剂量(每日剂量可不同),日剂量组按每日固定剂量给予华法林。研究主要终点包括两组INR达到稳定时间(连续3次INR达标≥2次)、INR在目标范围时间的百分比(TTR)、TTR达标率、亚治疗(INR<1.5)和超治疗(INR>4)INR百分比,次要终点为随访期间血栓栓塞及出血事件的发生情况。结果:周剂量组和日剂量组INR稳定时每日平均剂量差异无统计学意义[(2.5±1.0)mg vs(2.7±1.1)mg,P=0.349]。周剂量组INR达到稳定的平均时间显著短于日剂量组[(11.7±11.9)周vs(19.3±19.1)周,P<0.01]。周剂量组平均TTR[(55.6%±26.0%)vs(45.0%±25.5%),P<0.01]、TTR达标率(45.1%vs 27.2%,P<0.05)均显著高于日剂量组。周剂量组亚治疗(18.3%vs 23.1%,P<0.01)和超治疗INR百分比(2.0%vs 3.0%,P=0.100)均低于日剂量组,但后者差异无统计学意义。周剂量组血栓栓塞事件(1.2%vs 9.9%,P<0.05)、总体不良事件(3.7%vs 17.3%,P<0.01)的发生率显著低于日剂量组,出血事件(2.4%vs 7.4%,P=0.269)虽也较日剂量组低,但差异无统计学意义。结论:对于非瓣膜性心房颤动患者,与华法林每日固定剂量给药策略相比,周剂量给药策略能显著提高抗凝治疗的疗效,更快地达到目标INR,降低不良事件的发生率。

Objectives:To evaluate the anticoagulant efficacy of warfarin considering two different administration strategies in patients with non-valvular atrial fibrillation.Methods:The patients with non-valvular atrial fibrillation and CHA2 DS2-VASc score≥2 points(female CHA2 DS2-VASc score≥3 points)were recruited in Ningbo Hospital,Zhejiang University School of Medicine,from January 2015 to January 2019.If international normalized ratio(INR)did not meet the standard after initial warfarin empirical treatment(2.5 mg/d)for one week,the patients were then randomly assigned to weekly-dosage group(n=82)or daily-dosage(n=81).The weekly-dosage strategy was adjusted the daily dose of warfarin according to the total weekly dose(different daily dose),The warfarin was prescribed at a fixed daily dose or a fixed weekly dose according to INR fluctuation for daily-dosage and weekly-dosage group,repectively.So the daily dose for weekly-dosage strategy may be different.The primary end points included the time of achieving target INR,percentage of time in target range of INR(TTR),the rate of TTR reaching target,frequency of subtherapy(INR<1.5)and supertherapy(INR>4).The secondary end points were thromboembolism and hemorrhage events during follow-up.Results:There was no significant difference in mean daily dosage of warfarin([2.5±1.0]mg vs[2.7±1.1]mg,P=0.349)between weekly-dosage group and daily-dosage group when INR was stable.Compared with daily-dosage group,TTR and TTR compliance rate in weekly-dosage group was significantly higher,respectively(both P<0.05).Additionally,the time of INR reaching stability was significantly shorter([11.7±11.9]weeks vs[19.3±19.1]weeks,P<0.01),and the subtherapeutic rate was lower than that in daily-dose group(18.3%vs 23.1%,P<0.01).The INR percentage of time at a supertherapeutic level in weekly-dosage group was lower than that in daily-dosage group(2.0%vs 3.0%,P=0.100).There was only one case occurred cerebral infarction and two cases of haemorrhage events in the weekly-dosage group,while there were 8 cases of embolism and 6 cases of haemorrhage in the daily-dosage group.The incidence of embolism events(1.2%vs 9.9%,P<0.05)and compound endpoint events(3.7%vs 17.3%,P<0.05)in the weekly-dosage group were significantly lower than that in the daily-dosage group.Conclusions:For patients with non-valvular atrial fibrillation,weekly-dosage strategy of warfarin prescription can significantly improves the efficacy of anticoagulation therapy,achieve the target INR faster and reduce the incidence of adverse reaction events compared with classic warfarin daily-dosage strategy.