Time in the Therapeutic Range During Warfarin Therapy in Japanese Patients With Non-Valvular Atrial Fibrillation - A Multicenter Study of Its Status and Influential Factors -

Abstract

Background: Time in the therapeutic range (TTR) assesses the appropriateness of international normalized ratio of prothrombin time (PT-INR) control during warfarin therapy. We examined the status of and the factors influencing TTR in Japanese patients with non-valvular atrial fibrillation (AF). Methods and Results:We enrolled 501 AF patients (mean age, 70±10 years; males 66%; mean CHADS2 score 2.0±1.2) taking warfarin for ≥2 years from 5 prefectures. The PT-INR therapeutic range was set up according to the 2008 Japanese Guideline. TTR was 64±25% for all patients and varied from 56% to 74% with the institution. Time below and above TTR was 31±26% and 5±7%, respectively. TTR was not affected by gender or antiplatelet co-administration. TTR in patients <70 and ≥70 years old was 46±23% and 77±17%, respectively (P<0.0001). TTR in patients with CHADS2 score ≤1 and ≥2 was 59±27% and 68±23%, respectively (P<0.0001). TTR in patients with warfarin doses <2.0, 2.0-4.9, and ≥5.0 mg/day was 72±22%, 63±25% and 48±24%, respectively (all P<0.001). Multivariate analysis revealed age and warfarin dose as independent predictors of TTR.Conclusions: TTR is generally high in Japan, although it varies with institutions. Most of the time spent out of therapeutic range is below the range. TTR is influenced by age presumably because of the low range recommendation for elderly patients, and by warfarin dose presumably because of physicians' anxiety about the hemorrhage risk. (Circ J 2011; 75: 2087 - 2094

Persistence of oral anticoagulants in japanese patients with atrial fibrillation: non-vitamin k antagonist oral anticoagulant versus warfarin

“…This may also mean that the time in the therapeutic range (TTR) in generally higher in Japan than other countries [17,18]. The previous Japanese guideline for pharmacotherapy of AF (JCS of NOAC treatment was the occurrence of adverse events, including bleeding events; this was similar to the findings for the Dresden cohort [8,11,12].…”

Introduction of Point-of-Care Testing in Japanese Outpatient Clinics Is Associated With Improvement in Time in Therapeutic Range in Anticoagulant-Treated Patients

“…18 Okumura et al reported that the average TTR at 5 Japanese centers for cardiovascular disease was 64%. 10 These findings indicate the need for the establishment of strategies to improve TTR in actual clinical practice.…”

“…During follow-up, warfarin dosage for patients with non-valvular AF was adjusted according to the Japanese Guidelines for Pharmacotherapy of Atrial Fibrillation to maintain INR at 2.0-3.0 and 1.6-2.6 for patients aged <70 years and ≥70 years, respectively. 10 Warfarin dosage for patients with mechanical heart valve(s) and mitral stenosis was also adjusted according to the Guidelines to maintain INR at 2.0-3.0. 10 For the present study, we used the PT-INR results obtained at least 3 months after the initiation of warfarin.…”

“…10 Warfarin dosage for patients with mechanical heart valve(s) and mitral stenosis was also adjusted according to the Guidelines to maintain INR at 2.0-3.0. 10 For the present study, we used the PT-INR results obtained at least 3 months after the initiation of warfarin. Patients who had an interval >100 days between 2 PT-INR measurements were excluded because the calculated TTR in such cases may not accurately reflect the quality of warfarin control.…”

“…10, 30 Okumura et al reported that TTR increased slightly, although not significantly, during the second year of treatment in a 2-year observation period. 10 In addition, Rose et al showed that TTR during an "experienced" period of warfarin therapy was higher than that during the "inception" period. 30 The improvements observed in the present study, however, were statistically significant, and we ensured that there was an interval of at least 3 months between the initiation of warfarin therapy and TTR measurements recorded in this study.…”