Details
The U.S. Food and Drug Administration (FDA) conducted this study to expand previous work examining the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOAC) for non-valvular atrial fibrillation (NVAF) in users aged 65 years and older. In a previous FDA study using US Medicare data, dabigatran and apixaban had a more favorable benefit−harm profile compared to rivaroxaban in users aged 65 years and older. It was decided to examine whether a similar benefit-harm profile persists in younger users. Before conducting the current study, findings from the Medicare study were replicated in patients aged 65 years and older in the Sentinel System (Medicare only) to determine study feasibility and to assess if findings were comparable across data sources and analytic approaches. Specifically, the current study examined the comparative effectiveness and safety of NOACs examining risk of bleeding (major extracranial bleeding (MEB), gastrointestinal bleeding (GIB), intracranial hemorrhage) and thromboembolic stroke in NOAC users with NVAF aged under 65 years.
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)- a finding that was not observed in the previous FDA study of patients aged 65 years and older.
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. Based on the study findings, FDA determined no regulatory actions were required.