Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists–naive patients with atrial fibrillation

Background: Vitamin K antagonists (VKAs) reduce cardiovascular events (CVEs) in atrial fibrillation (AF) when a time in therapeutic range (TiTR) >70% is achieved. Factors affecting the time to achieve the TR (TtTR) are unknown. Methods: Prospective observational study including 1,406 nonvalvular AF patients starting VKAs followed for a mean of 31.3 months (3,690 patient/year); TiTR, TtTR, and SAMe-TT ₂R ₂ score were calculated, and CVEs were recorded. Results: Median TtTR was 8.0 days (interquartile range 5.0-18.0). Patients with high TtTR (ie, >75th percentile) were more likely to be in AF than in sinus rhythm at entry (odds ratio [OR]: 1.423, P =.011). Median TiTR was 60.0%; low TiTR (below median) was associated with SAMe-TT ₂R ₂ score (OR: 1.175, P =.001), high TtTR (>75th percentile, OR: 1.357, P =.017), and number of international normalized ratio checks (OR: 0.998, P =.049). We recorded 113 CVEs (3.1%/y), with a higher rate seen in patients with TtTR >75th percentile compared to those below (log-rank test, P =.006). A multivariable Cox regression analysis showed that SAMe-TT ₂R ₂ score (hazard ratio [HR]: 1.331, P <.001), TtTR >75th percentile (HR: 1.505, P =.047), TiTR <70% (HR: 1.931, P =.004), number of international normalized ratio checks (HR: 0.988, P <.001), digoxin (HR: 1.855, P =.008), and proton-pump inhibitors (HR: 0.452, P <.001) were independently associated with CVEs. Conclusions: High TtTR is associated with poorer long-term quality of VKAs therapy. Patients with TtTR >18 days or with high SAMe-TT ₂R ₂ score should be considered for treatment with non–vitamin K oral anticoagulants.