JAMA Netw Open
Selective NSAIDs tied to less bleeding
Clinical Takeaway: When NSAIDs are necessary in patients with AF receiving DOACs, consider a COX-2–selective agent (e.g., celecoxib) over nonselective NSAIDs to potentially lower bleeding risk, while still weighing cardiovascular safety and individual patient factors.
Patients with atrial fibrillation (AF) on direct oral anticoagulants (DOACs) frequently need pain control, but NSAIDs raise bleeding risk. Identifying safer options could meaningfully reduce harm.
In this multinational cohort study of 30,240 adults with nonvalvular AF (mean age, 72 years), concomitant use of DOACs with COX-2–selective NSAIDs was associated with significantly lower bleeding risk than use with nonselective NSAIDs. Over 37,833 treatment episodes, 45.2% involved COX-2–selective agents and 54.8% nonselective NSAIDs.
The primary outcome—hospitalization for gastrointestinal bleeding—occurred less frequently with COX-2–selective NSAIDs, translating to a 37% relative risk reduction (pooled hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.46–0.87). Absolute rates were notably lower as well, with incidence rates of ~20–27 per 1000 person-years for COX-2 agents versus ~35–53 per 1000 person-years for nonselective NSAIDs across datasets.
Risk reductions extended beyond the GI tract. Non-GI bleeding was also significantly decreased (pooled HR, 0.54; 95% CI, 0.40–0.74), with incidence rates roughly halved compared with nonselective NSAIDs.
Notably, women appeared to derive greater benefit (HR, 0.50; 95% CI, 0.31–0.80) than men (HR, 0.85; 95% CI, 0.55–1.32), though interaction findings were exploratory. Results were consistent across age groups, DOAC types, and multiple sensitivity analyses.
“These findings suggest that COX-2–selective NSAIDs may retain their beneficial effects regarding GI bleeding during concomitant use with DOACs,” the authors reported.
Overall, the data reinforce that COX-2 selectivity may mitigate bleeding risk even in high-risk anticoagulated populations, offering a practical strategy when NSAID therapy cannot be avoided.
Source: Meinart FM, et al. (2026, May 26). JAMA Netw Open. Direct Oral Anticoagulants, COX-2-Selective NSAIDs, and Gastrointestinal Bleeding in Atrial Fibrillation