Variability of INR and its relationship with mortality, stroke, bleeding and hospitalisations in patients with atrial fibrillation

Abstract

Background – rationale for study Atrial fibrillation is associated with an increased risk of stroke and mortality which is reduced by treatment with Warfarin. The most commonly used tool to assess the effectiveness of warfarin therapy is the time in therapeutic Range (TTR) of International Normalised Ratio (INR) 2.0-3.0. Our aim was to study whether INR variability, as assessed by the standard deviation of transformed INR (SDT INR) is more prognostically important than the TTR. Methods and Results We studied 19,180 patients with atrial fibrillation on warfarin therapy to evaluate the association of TTR and that of SDT INR with all-cause mortality, stroke, bleeding and hospitalisation. The SDT INR was more prognostically important than the TTR. One standard deviation (SD) higher of SDT INR had a hazard ratio (HR) of 1.59 (95% CI 1.52-1.66) of mortality compared with 1.18 (95% CI 1.13-1.24) for one SD lower of TTR. For the other 3 events the HR was also higher for the SDT INR than for the TTR (stroke 1.30 (95% CI 1.22-1.39) vs. 1.06 (95% CI 1.00-1.13), bleeding 1.27 (95% CI 1.20-1.35) vs. 1.07 (95% CI 1.01-1.14) , hospitalisation 1.47 (95% CI 1.45-1.49) vs. 1.13 (95% CI 1.10-1.15). When both metrics were included in the same analysis only the SDT INR was of significant predictive value. Conclusions The SDT INR is a better predictor of mortality, stroke, bleeding and hospitalisation than the TTR in patients with atrial fibrillation receiving warfarin therapy.