A Comparison between TTR and FIR as a measure of the quality of anticoagulation in patients with atrial fibrillation

Abstract

Atrial fibrillation (AF) is a growing concern worldwide. In order to prevent AF-related adverse vascular events, adequate oral anticoagulation with warfarin is essential. The Rosendaal method to evaluate TTR (time in therapeutic range) has traditionally been used in clinical trials to assess quality of anticoagulation but it’s utility in clinical practice is increasingly being questioned due to its tedious method of calculation and inability to account for the duration spent in an out-of-range INR. Frequency in range (FIR) is being reassessed as to its value in view of it being easier to calculate. Aim We aimed to compare FIR and TTR (using the Rosendaal method) as a measure to assess the quality of anticoagulation with warfarin in patients with valvular and non-valvular AF at a tertiary South African hospital. Objectives Secondary objectives were to assess the predictive ability of FIR to categorize patients with a TTR≥65% as well as to compare the CHA²DS²-VASc and HASBLED scores to TTR and FIR. Methods We retrospectively analysed the INR values for a cohort of 102 patients over a two year period and calculated both individual and overall mean TTR and FIR. Paired samples t-test was used to compare the two parameters and the Bland-Altman method comparison plot to assess the agreement between them. Results The mean overall TTR was 58.1%±SD 16% and the mean FIR was 50.8%±SD 16.7%. The mean TTR was significantly higher than the mean FIR (p<0.0001). At the individual level, FIR was positively correlated with TTR in a linear fashion (r= 0.93, 95% CI 0.90-0.95; p<0.001). However the Bland-Altman method plot indicated a lack of agreement between TTR and FIR, with a bias of 7.4% (95% CI: 6.1-8.6%) and limits of agreement -4.6% to 19.3%, standard deviation (s) = 6.1%. A cut off value of FIR≥53.3% was found to be a good predictor of TTR≥65%. Conclusion Our study shows that although TTR and FIR are highly correlated with the individual INR levels, they are not equal. The two methods cannot be used interchangeably to assess warfarin control and TTR should probably remain the gold standard.