Real-world evidence on off-label underdosing of direct oral anticoagulants in Asian patients with atrial fibrillation: prescribing patterns, determinants, and outcomes.
Off-label underdosing of direct oral anticoagulants (DOACs) is common among Asian patients with atrial fibrillation (AF), partly reflecting concerns about bleeding, yet Southeast Asian data remain limited. This study aimed to characterize DOAC dosing patterns, identify predictors of off-label underdosing, and evaluate associated effectiveness and safety outcomes.
We conducted a retrospective cohort using electronic health records (EHRs) from two tertiary hospitals in Thailand (2015-2023). Incident AF patients initiating dabigatran, rivaroxaban, apixaban, or edoxaban were included. Doses were classified as on-label, underdosed, or overdosed based on guideline criteria. Propensity score-based inverse probability of treatment weighting (PS-IPTW) Cox proportional hazards regression models was used to evaluate ischemic stroke or systemic embolism (ISSE) and bleeding outcomes.
Among 553 patients, 20.4% were underdosed, 6.3% overdosed, and 73.2% received on-label dosing. Rivaroxaban was most frequently underdosed. Older age and diabetes mellitus independently predicted underdosing. Compared to on-label dosing, underdosing was not associated with ISSE (adjusted hazard ratio [aHR] 0.48, 95% CI 0.11-2.16; p = 0.336) or bleeding (aHR 1.06, 95% CI 0.30-3.73; p = 0.924).
Off-label underdosing occurred in one-fifth of patients but was not associated with significant differences in ISSE or bleeding. Larger, prospective studies in broader Asian and non-Asian populations are warranted.
We conducted a retrospective cohort using electronic health records (EHRs) from two tertiary hospitals in Thailand (2015-2023). Incident AF patients initiating dabigatran, rivaroxaban, apixaban, or edoxaban were included. Doses were classified as on-label, underdosed, or overdosed based on guideline criteria. Propensity score-based inverse probability of treatment weighting (PS-IPTW) Cox proportional hazards regression models was used to evaluate ischemic stroke or systemic embolism (ISSE) and bleeding outcomes.
Among 553 patients, 20.4% were underdosed, 6.3% overdosed, and 73.2% received on-label dosing. Rivaroxaban was most frequently underdosed. Older age and diabetes mellitus independently predicted underdosing. Compared to on-label dosing, underdosing was not associated with ISSE (adjusted hazard ratio [aHR] 0.48, 95% CI 0.11-2.16; p = 0.336) or bleeding (aHR 1.06, 95% CI 0.30-3.73; p = 0.924).
Off-label underdosing occurred in one-fifth of patients but was not associated with significant differences in ISSE or bleeding. Larger, prospective studies in broader Asian and non-Asian populations are warranted.
Authors
Mongkhon Mongkhon, Koonlachad Koonlachad, Bvornphattanasakul Bvornphattanasakul, Phatthanasobhon Phatthanasobhon, Pholprasittito Pholprasittito, Wattanasombat Wattanasombat, Bureekam Bureekam
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