Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
AIM: To investigate the effects of off-label NOAC dose reduction compared to 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 2,466 patients (8.0%), compared to 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%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 to on-label standard dose users, while non-major bleeding risk appeared to be lower and mortality risk higher. Therefore, caution towards prescribing an off-label reduced NOAC dose is still required.
|ジャーナル名||British journal of clinical pharmacology|
|投稿者||van den Dries, Carline J; Pajouheshnia, Romin; van den Ham, Hendrika A; Souverein, Patrick; Moons, Karel G M; Hoes, Arno W; Geersing, Geert-Jan; van Doorn, Sander|
|組織名||Julius Center for Health Sciences and Primary Care, University Medical Center;Utrecht and Utrecht University, GA, Utrecht, the Netherlands.;Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for;Pharmaceutical Sciences, Utrecht University, the Netherlands.|