Safety of off‐label dose reduction of non‐vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Abstract

Aim To investigate the effects of off‐label non‐vitamin K oral anticoagulant (NOAC) dose reduction compared with on‐label standard dosing in atrial fibrillation (AF) patients in routine care. Methods Population‐based cohort study using data from the United Kingdom Clinical Practice Research Datalink, comparing adults with non‐valvular AF receiving an off‐label reduced NOAC dose to patients receiving an on‐label standard dose. Outcomes were ischaemic stroke, major/non‐major bleeding and mortality. Inverse probability of treatment weighting and inverse probability of censoring weighting on the propensity score were applied to adjust for confounding and informative censoring. Results Off‐label dose reduction occurred in 2466 patients (8.0%), compared with 18 108 (58.5%) on‐label standard‐dose users. Median age was 80 years (interquartile range [IQR] 73.0‐86.0) versus 72 years (IQR 66‐78), respectively. Incidence rates were higher in the off‐label dose reduction group compared to the on‐label standard dose group, for ischaemic stroke (0.94 vs 0.70 per 100 person years), major bleeding (1.48 vs 0.83), non‐major bleeding (6.78 vs 6.16) and mortality (10.12 vs 3.72). Adjusted analyses resulted in a hazard ratio of 0.95 (95% confidence interval [CI] 0.57‐1.60) for ischaemic stroke, 0.88 (95% CI 0.57‐1.35) for major bleeding, 0.81 (95% CI 0.67‐0.98) for non‐major bleeding and 1.34 (95% CI 1.12‐1.61) for mortality. Conclusion In this large population‐based study, the hazards for ischaemic stroke and major bleeding were low, and similar in AF patients receiving an off‐label reduced NOAC dose compared with on‐label standard dose users, while non‐major bleeding risk appeared to be lower and mortality risk higher. Caution towards prescribing an off‐label reduced NOAC dose is therefore required.