【作者】 刘艳霞；

【导师】 王祖禄；

【作者基本信息】 大连医科大学 ， 内科学， 2009， 硕士

【摘要】 目的:观察我国非瓣膜病房颤(NVAF)或房扑(AFL)患者应用不同起始剂量国产华法林时,在不同时间国际标准化比值(INR)的达标率,比较INR首次达标时间、INR达稳定时间及出血并发症的发生率等,以进一步了解国人应用国产华法林的最佳起始剂量,为临床进一步合理应用华法林提供更多证据。方法:入选2008年3月至2009年3月具有华法林抗凝适应证的NVAF或AFL患者共85例,随机分入起始剂量3.125mg组(第一组)28例,起始5mg,2天后改为3.125mg组(第二组)25例和起始5mg治疗组(第三组)32例。每日16时服用华法林钠(上海医药有限公司信谊制药总厂,国药准字H31022123),行AF经导管射频消融术(RFCA)的患者术后回病房后即服,次日起每日16时服。本组中AF术后患者2～4小时起以及其它血栓高危患者同时给予达肝素钠(5000～7500U,皮下注射,每12小时1次)4-7天,直至INR达到抗凝效果即1.6以上停用。于治疗第3、4、5、7、9天早晨8~10时测定INR,根据INR调整华法林剂量,每次增减量为0.625～1.25mg,直到INR稳定于1.8～3.0之间(服用同一剂量华法林,间隔一周INR稳定)。如INR>3.0时,暂停当日药物,每日监测INR,待INR<3.0时,华法林减量继续服用。如果连续2次INR在治疗范围,改为每周2次,1周后如果INR稳定,即可过渡到每周1次,如连续2次INR值稳定在目标范围之内,视为达到稳定,此时应用的华法林剂量为维持剂量,此后仍要每个月监测1次INR。INR达稳定后如再次超过目标范围,需复查INR,并寻找INR波动原因,如饮食结构改变、合并用药增减以及是否漏服药物等,确认后可适当增减剂量0.625～1.25mg,并重新按隔日测一次INR开始调整华法林剂量。随访1个月,观察三组在不同时间INR的达标率,三组患者INR首次达标时间,达稳定INR所需时间,发生INR增高(INR>3.0)次数,主要出血/血栓栓塞事件的差异等。结果:入选85例患者有1例患者于RFCA后第4天出现黑便、血红蛋白下降而终止应用华法林,当时INR为1.41,考虑非华法林所致,实际入选84例。三组基线特征(包括年龄、性别、身高、体重、联合用药、伴随疾病、服药前INR值等基线情况)无统计学差异。三组在第3天和第9天达标率无显著差异,第4、5和7天时第三组比第一、二组达标率明显增高(P<0.05),第二组比第一组达标率略高,但无统计学差异(P>0.05)。三组达标时间分别为8.2±2.4天;7.6±3.1天及6.2±2.1天,稳定时间分别为15.5±2.8天;14.8±3.1天及13.0±2.0天,第三组比第一、二组提早达标并稳定(P<0.05),第一、二组间无统计学差异(P>0.05)。第一组和第三组各有一例轻微出血(牙龈或结膜下少量出血),经停药及减量后无继续出血。三组均无明显出血及血栓栓塞事件,INR增高发生率亦无显著差异(P>0.05)。结论:对于中国NVAF或AFL患者,以5mg为初始剂量应用国产华法林能使INR安全、迅速、有效地达标并稳定。服药前3天可不必监测INR,于第4天起测INR,如达标则根据INR值减量至2.5～3.125mg,以后隔日测INR;如未达标,于第5、7天再测INR,此时如果达标,华法林则根据INR值减量至2.5～3.75mg。如果1周内仍未达标,表明该患者应用华法林的维持量应较大,达标后应维持达标剂量而不应减量,达标后监测时间可逐渐延长,但至少应每月监测一次。更多还原

【Abstract】 Objective: To investigate the effect of different initial warfarin dosages on the time of target international normalized ratio (INR) and the safety during dose adjustment in patients with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL).Methods: 85 patients with NVAF or AFL who had the indication of anticoagulation therapy were randomly assigned to three groups according to different initial warfarin dosages, 3.125 mg/d (Group 1), 3.125mg/d after 5 mg/d for tow days (Group 2) and 5 mg/d (Group 3). Baseline data collected included demographic characteristics (age, sex, height, weight), conjoined medication, assident diseases, and the INR before taking warfarin. Warfarin should be administered at 16:00 daily except for the patients following an AF radiofrequency current catheter ablation (RFCA) who should take warfarin come back ward. Low-molecular-weight heparin (LMWH 5000～7500U every 12 hours by subcutaneous injection) can be restarted 2-4 hours postoperatively along with warfarin and the combination continued for 4 to 7 days until the INR increase to the desired range (>1.6). If patients are considered to be at high risk of postoperative bleeding, LMWH can be delayed for 24 hours or longer. The INR was measured on the 3rd、4th、5th、7th and 9th day before 10:00 am, the dose of warfarin was adjusted according to INR, until INR was stabilized between 1.8 and 3.0 for at least one week at the same dose of warfarin. When the INR is above the therapeutic range 3.0 but less than 5.0, the patient has not developed clinically significant bleeding, the next dose of warfarin can be omitted and resumed (at a lower dose) when the INR approaches the desired range (<3.0). The INR is usually checked every other day until the therapeutic range has been reached and sustained for 2 times, then 2 times weekly for 1 week, then less often, according to the stability of the results. Once the INR becomes stable, the frequency of testing can be reduced to intervals as long as 4 weeks. Some patients on long-term warfarin therapy experience unexpected fluctuations in dose-response due to changes in diet, concurrent medication changes or poor compliance. When dose adjustments are confirmed and required, frequent monitoring is resumed. Follow up one month, to observe the INR change with different warfarin dose in patients with NVAF or AFL,and to compare the time that INR stabilized at target range,the ratio within stabilized target range at different days, and the incidence of bleeding episodes during the dose adjustment.Results: One patient occured dark stools and decrease of Hb as to terminate to take warfarin. It’s independence of warfarin because INR was 1.41. Actually 84 patients were selected. There was no significant difference on baseline data collected included demographic characteristics (age, sex, body height weight) , conjoined medication, assident disease , and the INR before taking warfarin in the 3 groups (P>0.05). Compared with group 1 and group2, the INR change in group3 was more quickly, the ratios of INR within target range on day 4, 5and day 7 were the highest (P<0.05) and the ratios in the group 2 was higher than group 1, but there was no significant statistic difference in group 1 and 2 (P>0.05). The mean time achieving the target INR was 8.2±2.4 days, 7.6±3.1 days and 6.2±2.1 days and reach a stabilized target INR was 15.5±2.8, 14.8±3.1 and 13.0±2.0 respectively in Group 1, 2 and 3. Compared with group 1 and group 2, the mean time achieving and reaching the stabilized target INR in group 3 was the shortest (P<0.05) and the INR in group 2 is shorter than group1, but no significant statistic difference (P>0.05). There was no significant difference on the incidence of exorbitant INR in three groups. There were not thromboembolism and important hemorrhage complication in 3 groups (P>0.05).Conclusions: In Chinese patients with NVAF or AFL who had the indication of anticoagulation therapy,an initial warfarin dosage of 5 mg/d treatment may reach the stabilized INR range quickly, safety and efficiently without increasing the bleeding complication.It’s not necessary to measure INR in the first 3 days. If INR reaches target range at 4th day,warfarin should be decreased to 2.5～3.125mg according to INR, and INR should be mearsured every other day. If INR is lower than target, INR should be measured at the 5th day and the 7th day until the therapeutic range has been reached, and then warfarin should be decreased to 2.5～3.75mg according to INR. It’s indicated that the maintenance dose of warfarin is higher if INR not yet reach target range at the 4th day. It’s not ought to decease dose of warfarin after INR reach target range. Once the INR becomes stable, the frequency of testing can be reduced to intervals as long as 4 weeks.更多还原