Reduced Time in Therapeutic Range and Higher Mortality in Atrial Fibrillation Patients Taking Acenocoumarol

Abstract Purpose The efficacy and tolerability of vitamin K antagonists (VKAs) depends on the quality of anticoagulant control, reflected by the mean time in therapeutic range (TTR) of international normalized ratio 2.0 to 3.0. In the present study, we aimed to investigate the association between TTR and change in TTR (ΔTTR) with the risk of mortality and clinically significant events in a consecutive cohort of atrial fibrillation (AF) patients. Methods We included 1361 AF patients stable on VKAs (international normalized ratio 2.0−3.0) during at least the previous 6 months. After 6 months of follow-up we recalculated TTR, calculated ΔTTR (ie, the difference between baseline and 6-month TTRs) and investigated the association of both with the risk of mortality and “clinically significant events” (defined as the composite of stroke or systemic embolism, major bleeding, acute coronary syndrome, acute heart failure, and all-cause deaths). Findings The median ΔTTR at 6 months of entry was 20% (interquartile range 0−34%), 796 (58.5%) patients had a TTR reduction of at least 20%, while 330 (24.2%) had a TTR P = 0.002) or sustained clinically significant events (28% vs 20%; P = 0.022). Based on Cox regression analyses, the overall risk of mortality at 6 months for each decrease point in TTR was 1.02 (95% CI, 1.01−1.04; P = 0.003), and the risk of clinically significant events was 1.01 (95% CI, 1.00−1.03; P = 0.028). Patients with TTR P = 0.002) and clinically significant events (hazard ratio = 1.71; 95% CI, 1.01−2.88; P = 0.046). Implications Our findings suggest that in AF patients anticoagulated with VKAs, a change in TTR over 6 months (ie, ΔTTR) is an independent risk factor for mortality and clinically significant events. Even in a cohort with good anticoagulation control, the risk for mortality and clinically significant events increases with every point deterioration of TTR.