OC 71.1 - Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Wednesday, July 13, 2022

10:15 AM – 10:30 AM

Location: ExCel Center, S11B

Presentation Format: In-Person

Co-Author(s)

CV

Carline J. Van Den Dries

MD, PhD
Julius Center for Health Sciences and Primary Care, UMC Utrecht/Utrecht University
Utrecht, Utrecht, Netherlands
RP

Romin Pajouheshnia

Assistant professor
Utrecht University
Utrecht, Utrecht, Netherlands
Rv

Rianne van den Ham

Assistant professor
Utrecht University
Utrecht, Utrecht, Netherlands
PS

Patrick Souverein

Assistant professor
Utrecht University
Utrecht, Utrecht, Netherlands
CM

Carl Moons

Professor of Clinical Epidemiology
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
Utrecht, Utrecht, Netherlands
AH

Arno Hoes

Prof, MD, PhD
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Utrecht, Utrecht, Netherlands
Geert-Jan Geersing, MD, PhD

Associate Professor
Department General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Utrecht, Utrecht, Netherlands

Presenting Author(s)

Sander van Doorn, MD, PhD

MD, PhD
University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Utrecht, Utrecht, Netherlands

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.