P4759Factors associated with inappropriate under-dosing of non-vitamin k antagonist oral anticoagulants (NOACs) by labelling criterion in patients with non-valvular atrial fibrillation in the UK
Authors: Garcia Rodriguez L A , Vora P , Brobert G , Lenz Y , Ruigomez A 
Published: October 2019

Abstract

Background
Current labelling for NOACs considers dose adjustments based on renal function and for some also patients' age, weight, comorbidities, and concomitant treatments. There is limited data on factors associated with inappropriately underdosing of NOACs according to the label in routine care.

Purpose
To assess factors associated with inappropriate underdosing among patients initiating treatment with NOACs for NVAF in the United Kingdom (UK) general practice by applying respective EU labelling criterion.

Methods
This retrospective cohort study utilized data from The Health Improvement Network and Clinical Practice Research Datalink in the UK. New users of NOACs aged ≥18 years with ≥1-year enrolment in the databases from Jan 2011 - Dec 2016 were included. Three mutually exclusive cohorts of new users of apixaban, dabigatran and rivaroxaban with NVAF were identified with the date of prescription being the index date. Patients with any recent record (within 3 months) of other indications (DVT, PE or hip/knee surgery) were excluded. Appropriate and inappropriate underdosing were defined based on the criterion in the EU label of individual NOACs.

Results
There were 30,467 new users of NOACs with NVAF during the study period. Of these, 23,444 new users of NOACs received an appropriate dose based on label recommendations. They were 4,953 new users who were inappropriately under-dosed (29.4% in apixaban, 8.7% in dabigatran and 9.1% in rivaroxaban.
Older age (70+) was a strong predictor of inappropriate underdosing among apixaban (odds ratio (OR) 7.3; 95% CI: 5.6–9.6) and rivaroxaban (OR 2.8; 95% CI: 2.1–5.4) but not for dabigatran users (OR 0.4; 95% CI: 0.3–0.6). Female apixaban and rivaroxaban users were at greater risk of inappropriate underdosing.
For all three NOACs, inappropriate underdosing was less frequent in recent years. Inappropriate underdosing was more frequent among new users with antecedents of intracranial bleed. Inappropriate underdosing was more frequent in apixaban users with a history of ischaemic stroke and rivaroxaban users with history of Ischaemic heart disease. There was no inappropriate underdosing among all new users of NOACs with eGFR under 30. 25.5% of apixaban users and less than 0.5% of rivaroxaban new users with eGFR between 30 and 50 were inappropriately under-dosed. Frailty was a predictor of inappropriate underdosing among apixaban and rivaroxaban new users and the risk increased with greater level of frailty. CHA2DS2VASc score of ≥4 in apixaban users and increasing HAS-BLED scores in apixaban and dabigatran users were significantly associated with inappropriate underdosing but not in rivaroxaban.

Conclusions
Apixaban had the highest proportion of patients who were inappropriately under-dosed compared to other NOACs. Different factors associated with inappropriate dosing from this study would inform about the factors that are taken into consideration before prescribing different doses of NOACs.

Acknowledgement/Funding
The study is funded by Bayer AG