A cohort study in the FDA Sentinel System of >173,000 NVAF patients aged 21-64 found that rivaroxaban was associated with higher major extracranial bleeding (HR 1.91) and gastrointestinal bleeding (HR 1.92) versus apixaban, with no difference in thromboembolic stroke. Dabigatran carried a higher thromboembolic stroke risk than both rivaroxaban and apixaban. Apixaban emerged with the most favourable benefit-harm profile — extending Medicare findings into a younger AF population.
To compare major extracranial bleeding (MEB), gastrointestinal bleeding (GIB), intracranial hemorrhage (ICH), and thromboembolic stroke in individuals aged younger than 65 years using non-vitamin K oral anticoagulants (NOAC users) for nonvalvular atrial fibrillation (NVAF). DESIGN, SETTING, AND PARTICIPANTS: This cohort study using health care claims data between October 2010 and February 2022 in the FDA Sentinel System included standard dose NOAC (rivaroxaban, apixaban, and dabigatran) users with NVAF aged 21 to 64 years. Analyses conducted between December 2022 and August 2023. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) and 95% CIs were estimated for each outcome (MEB, GIB, ICH, and thromboembolic stroke) in inverse probability of treatment-weighted pairwise comparisons: rivaroxaban vs apixaban, rivaroxaban vs dabigatran, and dabigatran vs apixaban.
A total of more than 173 000 patients (mean [SD] age, 56.6 [7.23] years; 27.5% female; 72.5% male) were included across the 3 exposure cohorts. The number of NOAC users for each pairwise comparison were rivaroxaban (57 932) vs apixaban (96 057), rivaroxaban (57 399) vs dabigatran (20 188), and dabigatran (20 163) vs apixaban (96 668). Rivaroxaban was associated with higher risks of MEB and GIB compared with apixaban (MEB: HR, 1.91; 95% CI, 1.56-2.34; GIB: HR, 1.92, 95% CI, 1.54-2.39), while differences in thromboembolic stroke prevention were not significant (HR, 1.05; 95% CI, 0.77-1.44). Dabigatran was associated with higher thromboembolic stroke risk (rivaroxaban vs dabigatran: HR, 0.61; 95% CI, 0.39-0.94; dabigatran vs apixaban: HR, 1.74; 95% CI, 1.13-2.68).
These findings suggest that for patients aged younger than 65 years treated with NOACs for NVAF, apixaban was associated with the most favorable benefit-harm profile. While the results suggest that rivaroxaban may have provided greater stroke prevention than dabigatran, it was associated with higher bleeding risks than apixaban without additional stroke prevention. The higher thromboembolic stroke risks observed with dabigatran in younger patients suggest important age-related differences in effectiveness that warrant further investigation.
