Apixaban Shows Best Benefit–Risk Profile in Younger Non-Valvular AF Patients: JAMA
Researchers have found in a new study among patients under 65 years treated with NOACs for nonvalvular atrial fibrillation, apixaban demonstrated the most favorable balance of efficacy and safety. Rivaroxaban showed greater stroke prevention than dabigatran but carried a higher bleeding risk without added benefit over apixaban. Dabigatran was associated with higher thromboembolic stroke risk in younger patients, highlighting potential age-related differences in effectiveness. The study was published in JAMA Network Open by Marie C. and colleagues.
The current study is a well-conducted cohort study conducted through an extensive analysis of the healthcare claims database for over a decade, starting from October 2010 until February 2022. Specifically, the analysis included patients who used NOAC in standard doses, especially rivaroxaban, apixaban, and dabigatran. The study period was from December 2022 to August 2023. Inverse probability of treatment weighting was employed to conduct pairwise comparison among the drugs involved in the study.
Key findings:
- The number of patients in the study was greater than 173,000 with an average age of 56.6 years (standard deviation ±7.23).
- The majority of the subjects included in the study was male, with their proportion being 72.5%, while the remaining 27.5% was females.
- In order to make the comparisons, the subjects were categorized into the following pairwise comparison groups: Rivaroxaban (n=57,932) vs Apixaban (n=96,057); Rivaroxaban (n=57,399) vs Dabigatran (n=20,188); Dabigatran (n=20,163) vs Apixaban (n=96,668).
- Particularly, the hazard ratio (HR) value for Major Extracranial Bleeding (MEB) was 1.91 (95% confidence interval [CI], 1.56-2.34), while for Gastrointestinal Bleeding (GIB), it was 1.92 (95% CI, 1.54-2.39).
- However, despite the much higher risks, there was no statistically significant difference between the prevention of thromboembolic stroke among patients treated with rivaroxaban and apixaban. The HR was equal to 1.05 (95% CI, 0.77-1.44).
- However, while considering dabigatran with the rest of the anticoagulants, the outcomes leaned towards the safety aspect. The risk of thromboembolic stroke was greater for dabigatran.
- In contrast, when rivaroxaban was compared to dabigatran, rivaroxaban had a better result in stroke prevention (HR, 0.61; 95% CI, 0.39-0.94). On the other hand, when dabigatran was compared to apixaban, dabigatran had an increased stroke risk (HR, 1.74; 95% CI, 1.13-2.68).
The authors thus found that the less favorable effect profile associated with rivaroxaban observed in elderly individuals is also observed in individuals under the age of 65 years. It appears from the findings of the study that although rivaroxaban provides more benefits compared to dabigatran regarding stroke prevention, the high risks of bleeding associated with rivaroxaban compared to apixaban without any added stroke-prevention benefits make apixaban a better choice.
Reference:
Bradley MC, Simon AL, Kolonoski J, Graham DJ, Zhang R, Connolly JG. Stroke and Bleeding Risks With Non–Vitamin K Oral Anticoagulants in Nonvalvular Atrial Fibrillation. JAMA Netw Open. 2026;9(4):e269082. doi:10.1001/jamanetworkopen.2026.9082
