Is naproxen (Nonsteroidal Anti-Inflammatory Drug) safe for patients with a history of stroke who are taking Eliquis (apixaban), an anticoagulant?

Naproxen Safety in Post-Stroke Patients on Eliquis

Naproxen should be avoided in patients with a history of stroke who are taking Eliquis (apixaban), as NSAIDs significantly increase bleeding risk when combined with anticoagulants and may increase stroke recurrence risk.

Primary Concern: Bleeding Risk

The combination of NSAIDs like naproxen with anticoagulants creates a compounding bleeding risk that outweighs any potential benefits:

• NSAIDs increase hemorrhagic stroke risk independently. Naproxen specifically has been associated with increased risk of hemorrhagic stroke (HR 2.15,95% CI 1.35-3.42) 1.

• Concurrent use of antiplatelet or anticoagulant medications with NSAIDs is a documented predictor of inappropriate prescribing and bleeding complications 2. The European Society of Cardiology explicitly identifies "parallel intake of antiplatelet therapy, chronic concomitant use of non-steroidal anti-inflammatory drugs" as factors that "need to be taken into account with regard to an increased bleeding risk—especially gastro-intestinal bleedings" 2.

• Post-stroke patients on anticoagulation are already at elevated bleeding risk. Guidelines recommend apixaban specifically for patients with prior bleeding history due to its lower bleeding profile compared to warfarin 2, but adding an NSAID negates this safety advantage.

Secondary Concern: Stroke Recurrence

While the evidence on naproxen and ischemic stroke is somewhat mixed, the risk profile is concerning:

• One large population-based study found no increased ischemic stroke risk with naproxen (OR 0.68,95% CI 0.36-1.29) 3, suggesting it may be safer than other NSAIDs like diclofenac for ischemic events.

• However, another study in healthy individuals found naproxen associated with increased hemorrhagic stroke risk 1, which is particularly relevant for anticoagulated patients.

• The overall meta-analysis data shows NSAIDs as a class increase hemorrhagic stroke risk (pooled RR 1.332,95% CI 1.105-1.605) 4.

Clinical Algorithm for Pain Management

For post-stroke patients on apixaban requiring analgesia:

1. First-line: Acetaminophen (paracetamol) - Does not increase stroke risk even in patients with high cardiovascular risk (OR 0.97,95% CI 0.85-1.10) 3 and lacks antiplatelet effects.

2. Second-line: Topical NSAIDs or non-pharmacologic approaches - Minimize systemic NSAID exposure.

3. Avoid: All oral NSAIDs - Particularly naproxen, ibuprofen, and diclofenac in anticoagulated patients.

4. If NSAID absolutely necessary: Use the lowest effective dose for the shortest duration possible, with close monitoring for bleeding complications and consideration of temporary anticoagulation adjustment in consultation with neurology/cardiology 2.

Critical Pitfalls to Avoid

• Do not assume naproxen is "safer" because it's available over-the-counter. The hemorrhagic stroke data is concerning 1, 4.

• Do not rely on the patient's stroke being "old" or "stable." Post-stroke patients remain at elevated risk for both recurrent ischemic and hemorrhagic events, and anticoagulation is specifically indicated for this ongoing risk 2.

• Do not overlook gastrointestinal bleeding risk. This is the most common site of major bleeding with NSAID-anticoagulant combinations 2.