Real-world evidence on off-label underdosing of direct oral anticoagulants in Asian patients with atrial fibrillation: prescribing patterns, determinants, and outcomes
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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. This study was conducted because doctors sometimes prescribe lower-than-recommended doses of direct oral anticoagulants (DOACs) for people living with atrial fibrillation (AF), especially in Asian populations, due to concerns about bleeding. However, it is unclear how often this happens in real-world practice in Thailand, what factors influence these decisions, and whether using lower doses affects patient outcomes such as stroke or bleeding. The researchers used electronic health records (EHRs) from two hospitals in Thailand to follow 553 people newly diagnosed with AF who started DOAC treatment between 2015 and 2023. They found that most people (about 73%) received recommended doses, but around 20% received lower-than-recommended doses, most commonly rivaroxaban. Older age and having diabetes were linked to a higher likelihood of receiving a lower dose. Importantly, when comparing people who received lower doses with those who received recommended doses, there were no meaningful differences in the risks of stroke or bleeding. These results suggest that although prescribing lower doses is relatively common, it may not provide clear benefits or harms in terms of major clinical outcomes. This highlights the need for careful, individualized decision-making rather than routine dose reduction based on concern alone. This study adds important real-world evidence from Southeast Asia, where data are still limited. It helps clinicians, researchers, and policymakers better understand prescribing patterns and supports the need for larger studies to guide safe and effective DOAC use across diverse populations. Older age and diabetes independently predicted off-label underdosing, with rivaroxaban being the most frequently underdosed agent.While 73% received on-label DOACs, a significant 20.4% were prescribed off-label underdoses, highlighting a persistent clinical trend in Asian patients.Off-label underdosing showed no statistically significant difference in risks for ischemic stroke, systemic embolism, or bleeding compared to on-label regimens.These findings highlight the need for larger, multicenter real-world studies to confirm clinical outcomes and inform individualized DOAC dosing strategies. Older age and diabetes independently predicted off-label underdosing, with rivaroxaban being the most frequently underdosed agent. While 73% received on-label DOACs, a significant 20.4% were prescribed off-label underdoses, highlighting a persistent clinical trend in Asian patients. Off-label underdosing showed no statistically significant difference in risks for ischemic stroke, systemic embolism, or bleeding compared to on-label regimens. These findings highlight the need for larger, multicenter real-world studies to confirm clinical outcomes and inform individualized DOAC dosing strategies.
Source: Figshare
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7172261069