Are nonsteroidal anti-inflammatory drugs (NSAIDs) safe to use in an older adult patient with non-valvular atrial fibrillation who is taking Eliquis (apixaban), a blood thinner?

NSAIDs Should Be Avoided in Patients Taking Eliquis Due to Significantly Increased Bleeding Risk

NSAIDs are not safe in patients on Eliquis (apixaban) and should be avoided whenever possible, as concomitant use nearly doubles the risk of hospital-diagnosed bleeding events. 1

Evidence of Bleeding Risk

The most recent and highest quality evidence demonstrates substantial harm:

• A 2025 nationwide cohort study of 114,119 AF patients found that NSAID use with apixaban increased bleeding risk more than two-fold (adjusted HR 2.15; 95% CI 1.70-2.72). 1

• The absolute bleeding rate increased from 3.9 per 100 person-years without NSAIDs to 6.2 per 100 person-years with NSAIDs, meaning you would harm 1 patient for every 43 treated for one year. 1

• Gastrointestinal bleeding risk specifically increased 2.3-fold overall with NSAID use across all anticoagulants. 1

Guideline Recommendations

European Society of Cardiology guidelines explicitly identify NSAIDs as a correctable bleeding risk factor that should be addressed in anticoagulated AF patients (Class IIa, Level A recommendation). 2

• NSAIDs are specifically listed in the HAS-BLED bleeding risk score as a modifiable risk factor requiring intervention. 2

• American Family Physician guidelines warn that combining NSAIDs with anticoagulants increases bleeding risk 3-6 fold and causes INR increases up to 15% (though this data is from warfarin studies). 2

Types of Bleeding Increased

NSAID use with apixaban increases multiple bleeding types:

• Gastrointestinal bleeding (most common) 1
• Urinary tract bleeding (aHR 1.48) 1
• Thoracic/respiratory tract bleeding (aHR 1.59) 1
• Anemia caused by bleeding (aHR 3.50) 1

Clinical Management Algorithm

If NSAIDs are absolutely necessary:

1. Reassess whether NSAID use is truly required - this should be done at every clinical encounter. 3

2. Consider alternative pain management such as acetaminophen, which does not increase bleeding risk. 2

3. If NSAIDs cannot be avoided, add proton pump inhibitor (PPI) therapy - the risk of upper GI bleeding without PPI protection is dramatically higher (aOR 2.47 for NSAIDs without PPI). 4

4. Use the shortest duration and lowest effective NSAID dose possible. 3

5. Increase monitoring frequency - patients require regular clinical review for bleeding signs when NSAIDs are used. 3, 4

6. Calculate and document HAS-BLED score - NSAID use adds 1 point; scores ≥3 indicate high bleeding risk requiring caution and regular review. 2

Important Caveats

• The bleeding risk applies to all NSAID subtypes, not just specific agents. 1

• Among direct oral anticoagulants, apixaban showed the second-highest bleeding risk with NSAIDs (after edoxaban), higher than dabigatran or warfarin. 1

• A 2020 Korean study found that concomitant NSAID use with NOACs increased bleeding risk by 41% (aOR 1.41; 95% CI 1.24-1.61). 4

• Expert reviews emphasize that NSAIDs in anticoagulated AF patients carry risk not only for bleeding but also for thromboembolism. 3

Bottom Line for Clinical Practice

The evidence is clear and consistent: NSAIDs should be considered contraindicated in patients on apixaban unless the clinical benefit clearly outweighs the substantial bleeding risk. When NSAIDs are unavoidable, mandatory PPI co-prescription and intensified bleeding surveillance are required. 2, 3, 4, 1