Effect of Temporary Interruption of Warfarin Due to an Intervention on Downstream Time in Therapeutic Range in Patients With Atrial Fibrillation (from ORBIT AF)

Abstract

The aim of this study was to quantify time in therapeutic range (TTR) before and after a temporary interruption of warfarin due to an intervention in the Outcomes Registry for Better Informed Treatment of atrial fibrillation (AF). AF patients on warfarin who had a temporary interruption followed by resumption were identified. A nonparametric method for estimating survival functions for interval censored data was used to examine the first therapeutic International Normalized Ratio (INR) after interruption. TTR was compared using Wilcoxon signed rank test. Cox proportional hazards model was used to investigate the association between TTR in the first 3 months after interruption and subsequent outcomes at 3 to 9 months. Of 9,749 AF patients, 71% were on warfarin. Over a median (IQR) follow-up of 2.6 (1.8 to 3.1) y, 33% of patients had a total of 3,022 temporary interruptions. The first therapeutic INR was recorded within 1 week in 35.0% (95% confidence interval 32.6% to 37.4%), 2 weeks in 54.6% (52.2% to 57.0%), 30 days in 70.0% (67.9% to 72.1%) and 90 days in 91.3% (90.0% to 92.5%) of patients. Compared with pre-interruption, TTR 3 months after interruption was significantly lower (61.1% [36.6% to 85.0%] vs 67.6% [50.0% to 81.3%], p <0.0001). A 10 unit increment in the TTR in the first 3 months after interruption was associated with a lower risk of major bleeding [Hazard ratio 0.91 (0.85 to 0.97), p = 0.005]. This association was noted in patients who received bridging anticoagulation, but not in those who did not. In conclusion, temporary interruption of warfarin is common, and nearly half of these patients had subtherapeutic INR after 2 weeks. Lower TTR in the first 3 months after interruption was associated with higher incidence of major bleeding in patients who received bridging anticoagulation.