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

1Julius Center for Health Sciences and Primary Care, UMC Utrecht/Utrecht University, Utrecht, Utrecht, Netherlands, 2Utrecht University, Utrecht, Utrecht, Netherlands, 3UMC Utrecht/Utrecht University, Utrecht, Utrecht, Netherlands, 4Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, Utrecht, Utrecht, Netherlands, 5University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands, Utrecht, Utrecht, Netherlands

Abstract Number: OC 71.1

Meeting: ISTH 2022 Congress

Theme: Arterial Thromboembolism » Atrial Fibrillation

Background: While non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly prescribed, concerns have emerged about patients receiving a lower dose against guideline recommendations, i.e. off-label dose reduction. The clinical impact of off-label dose reduction remains unclear.

Aims: 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 bleeding, non-major bleeding and mortality. Inverse probability of treatment weighting (IPTW) on the propensity score was applied to adjust for confounding.

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). IPTW resulted in an adjusted hazard ratio of 1.07 (95%CI 0.65-1.74) for ischaemic stroke; 0.98 (95%CI 0.65-1.48) for major bleeding; 0.89 (95%CI 0.74-1.08) for non-major bleeding; and 1.48 (95%CI 1.25-1.76) for mortality.

Conclusion(s): In this large population-based study, the risk of ischaemic stroke, non-major bleeding and major bleeding was similar in AF patients receiving an off-label reduced NOAC dose compared to on-label standard dose users, while mortality risk appeared to be higher. Therefore, altogether, off-label dose reduction seems unlikely to be a fruitful strategy when aiming to reduce bleeding risk in (high-risk) AF patients.

Figure 1.

Forest plot showing the main results, comparing off-label dose reduction to on-label standard dosing. Event rates are incidence rates per 100 person years. ATT= average treatment effect among the treated.

To cite this abstract in AMA style:

Van Den Dries C, Pajouheshnia R, van den Ham R, Souverein P, Moons C, Hoes A, Geersing G, van Doorn S. Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation [abstract]. https://abstracts.isth.org/abstract/safety-of-off-label-dose-reduction-of-non-vitamin-k-antagonist-oral-anticoagulants-in-patients-with-atrial-fibrillation/. Accessed September 22, 2023.

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