Apixaban had best benefit-harm profile under 65
In adults younger than 65 with atrial fibrillation, apixaban had lower bleeding risk than rivaroxaban with similar stroke prevention, and dabigatran had higher stroke risk than apixaban.
*Observational cohort study; Level 2b (OCEBM).

Citation

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 Network Open. 2026;9(4):e269082. doi:10.1001/jamanetworkopen.2026.9082

Background

Older studies suggested rivaroxaban may cause more bleeding than other newer blood thinners in older adults with atrial fibrillation, but it was unclear if this holds for younger adults.

Patients

Adults aged 21 to 64 years with nonvalvular atrial fibrillation starting standard-dose apixaban, rivaroxaban, or dabigatran in US insurance claims (2010-2022). Excluded: prior blood thinner use, dialysis or kidney transplant, valve disease/repair, recent institutional stay, or other reasons for anticoagulation.

Intervention

Rivaroxaban or dabigatran (standard doses).

Control

Apixaban or the alternative study drug (pairwise comparisons).

Outcome

Major bleeding outside the brain (including gastrointestinal bleeding), bleeding in the brain, and thromboembolic stroke.

Follow-up Period

Median 62 days.

Results

Comparison Outcome Relative risk over time
Rivaroxaban vs apixaban Major bleeding outside the brain (primary) HR 1.91 (95% CI, 1.56-2.34)
Rivaroxaban vs apixaban Gastrointestinal bleeding HR 1.92 (95% CI, 1.54-2.39)
Rivaroxaban vs dabigatran Thromboembolic stroke (primary) HR 0.61 (95% CI, 0.39-0.94)
Dabigatran vs apixaban Thromboembolic stroke (primary) HR 1.74 (95% CI, 1.13-2.68)
HR = hazard ratio; CI = confidence interval.
Follow-up was “as-treated” (patients were censored when they stopped or switched).

Limitations

Because this was not a randomized study, unmeasured differences between groups could partly explain results. Follow-up was short and event numbers were low; absolute risks were small, so relative differences may look larger than day-to-day patient impact.

Funding

US Food and Drug Administration task order; agency staff coauthored the manuscript.

Clinical Application

For atrial fibrillation patients under 65 needing a standard-dose newer blood thinner, prefer apixaban when appropriate; use extra caution with rivaroxaban bleeding risk and dabigatran stroke risk.