The Effect Of Different Initial Warfarin Dosages On The Time Of Target International Normalized Ratio In Patients With Nonvalvular Atrial Fibrillation Or Atrial Flutter

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.