Time in Therapeutic Range and Disease Outcomes in Elderly Japanese Patients With Nonvalvular Atrial Fibrillation

BACKGROUND: The relationship between warfarin treatment quality and prognosis for Japanese patients with nonvalvular atrial fibrillation (NVAF) has not been studied thoroughly. METHODS AND RESULTS: Data from the J-RHYTHM Registry were used to determine the time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time in elderly patients (≥70 years). Target INR was 1.6-2.6. Of 7,406 patients with NVAF in the database, 3,832 elderly patients (mean [±SD] age 77.0±5.0 years) constituted the study group. Of these patients, 459 did not receive warfarin and 3,373 received warfarin. Patients on warfarin were subdivided into 4 TTR groups: <40%, 40-59.9%, 60-79.9%, and ≥80%. During the 2-year follow-up, the incidence of thromboembolism and all-cause death was lower in patients with higher TTR (Ptrend<0.001); however, the incidence of major hemorrhage was higher in patients with TTR <40%. In multivariate analysis, compared with the no-warfarin group, TTR 60-79.9% and ≥80% were associated with lower thromboembolic risk, with hazard ratios (HR) of 0.34 (95% confidence interval [CI] 0.17-0.67; P=0.002) and 0.35 (95% CI 0.18-0.68; P=0.002), respectively, and lower all-cause death (HR 0.37 [95% CI 0.22-0.65; P<0.001] and 0.43 [95% CI 0.26-0.71; P=0.001], respectively). TTR <40% was associated with major hemorrhage (HR 5.57; 95% CI 2.04-15.25; P=0.001). CONCLUSIONS: In elderly Japanese patients with NVAF, TTR should be maintained ≥60% to prevent thromboembolism and all-cause death. TTR <40% should be avoided to prevent major hemorrhage.