Real-world evidence on off-label underdosing of direct oral anticoagulants in Asian patients with atrial fibrillation: prescribing patterns, determinants, and outcomes.
In this study, off-label underdosing of DOACs in Asian AF patients was common but did not significantly impact stroke or bleeding outcomes. Further research is needed.
Where it sits
this study against the rest of the ara 290 corpusSummary and findings
This study examined dosing patterns of direct oral anticoagulants (DOACs) in 553 Asian patients with atrial fibrillation, focusing on off-label underdosing. Older age and diabetes mellitus were identified as predictors of underdosing. Underdosing was not significantly associated with ischemic stroke or systemic embolism or bleeding compared to on-label dosing.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>p</i> = 0.336) or bleeding (aHR 1.06, 95% CI 0.30-3.73; <i>p</i> = 0.924).<h4>Conclusions</h4>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.
Background
The study addresses the clinical issue of off-label underdosing of direct oral anticoagulants (DOACs) in Asian patients with atrial fibrillation (AF), a practice partly driven by concerns about bleeding risks. Prior to this study, there was limited data on DOAC dosing patterns and outcomes in Southeast Asian populations. Understanding these patterns is crucial for optimizing anticoagulation therapy and improving patient outcomes.
Methods
This was a retrospective cohort study using electronic health records from two tertiary hospitals in Thailand, covering the period from 2015 to 2023. The study included incident AF patients who initiated treatment with dabigatran, rivaroxaban, apixaban, or edoxaban. Doses were categorized as on-label, underdosed, or overdosed based on established guidelines. The primary outcomes were ischemic stroke or systemic embolism (ISSE) and bleeding, analyzed using propensity score-based inverse probability of treatment weighting (PS-IPTW) Cox proportional hazards regression models.
Results
Among the 553 patients studied, 20.4% were underdosed, 6.3% overdosed, and 73.2% received on-label dosing. Rivaroxaban was the most frequently underdosed medication. Older age and diabetes mellitus were identified as independent predictors of underdosing. The analysis showed that underdosing was not significantly 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) compared to on-label dosing.
Interpretation
The findings suggest that while off-label underdosing of DOACs is relatively common in this population, it does not appear to significantly affect the risk of ischemic stroke, systemic embolism, or bleeding. This contrasts with concerns that underdosing might compromise efficacy or safety. However, the study's retrospective nature and limited geographic scope suggest that further research, particularly prospective studies in diverse populations, is necessary to confirm these findings and inform clinical practice.
Key findings
- 20.4% of patients were underdosed.
- 6.3% of patients were overdosed.
- 73.2% of patients received on-label dosing.
- Rivaroxaban was most frequently underdosed.
- Underdosing not associated with ISSE (aHR 0.48, 95% CI 0.11-2.16, p=0.336).
- Underdosing not associated with bleeding (aHR 1.06, 95% CI 0.30-3.73, p=0.924).
Limitations
- Retrospective design
- Limited to two hospitals in Thailand
- Potential lack of generalizability
- Short follow-up period
- Surrogate endpoints