Time in the therapeutic range during warfarin therapy in Japanese patients with non-valvular atrial fibrillation. - A multicenter study of its status and infuential factors-.

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.