Can Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) worsen aneurysms?

NSAIDs and Aneurysm Risk: A Complex Relationship

The effect of NSAIDs on aneurysms depends critically on the type of aneurysm and clinical context—for intracranial aneurysms, emerging evidence suggests NSAIDs may actually be protective by reducing inflammation-driven growth, while for patients with existing aneurysmal subarachnoid hemorrhage requiring surgery, NSAIDs with strong antiplatelet effects pose significant bleeding risks.

Intracranial Aneurysms (Unruptured)

Potential Protective Effects

• NSAIDs may reduce aneurysm growth and rupture risk by inhibiting inflammatory pathways that drive aneurysm progression, including nuclear factor-κB, tumor necrosis factor-α, and matrix metalloproteinases 1

• Inflammation with proinflammatory cytokine infiltration is a hallmark of intracranial aneurysm pathophysiology, making anti-inflammatory therapy theoretically beneficial 1

• Basic science and preclinical data support NSAIDs as a promising treatment strategy for preventing intracranial aneurysm progression 1

• A combination of low-dose aspirin with selective COX-2 inhibitors may offer therapeutic benefits with reduced side effects compared to either agent alone 1

Abdominal Aortic Aneurysms (AAA)

Evidence for Reduced Growth

• NSAIDs appear to slow AAA expansion rates significantly—patients taking NSAIDs had median growth of 1.8 mm/year versus 3.2 mm/year in matched controls not taking these drugs (p=0.004) 2

• Indomethacin reduces production of prostaglandin E2, IL-1β, and IL-6 in AAA tissue, all of which contribute to aneurysm wall degradation 2

• Prostaglandin E2 suppresses smooth muscle cell proliferation and increases apoptosis at concentrations found in AAA walls, suggesting its reduction may be beneficial 2

Critical Contraindications: Aneurysmal Subarachnoid Hemorrhage

Perioperative Bleeding Risk

• NSAIDs with prominent anti-inflammatory properties (like ketoprofen) significantly impair platelet function in patients with subarachnoid hemorrhage and should be avoided before aneurysm surgery 3

• Ketoprofen decreased maximal platelet aggregation before surgery and on postoperative day 3, with one patient developing postoperative intracranial hematoma 3

• For perioperative pain management in SAH patients, acetaminophen is safer as it does not impair platelet aggregation 3

Paradoxical Anti-Inflammatory Benefits Post-Rupture

• After aneurysmal SAH, cumulative NSAID use showed inverse correlation with IL-6 (r=-0.437, p<0.001) and CRP levels (r=-0.369, p<0.001), suggesting reduced inflammatory response 4

• Higher cumulative NSAID doses reduced odds of unfavorable outcome (Glasgow Outcome Scale 1-3) in SAH patients 4

• This creates a clinical dilemma: NSAIDs may reduce harmful inflammation post-SAH but increase bleeding risk perioperatively 3, 4

Cardiovascular Considerations

Increased Thrombotic Risk

• All NSAIDs carry FDA black box warnings for increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal 5

• This risk increases with duration of use and is higher in patients with existing cardiovascular disease or risk factors 5

• NSAIDs can worsen congestive heart failure and increase blood pressure 5

• Diclofenac shows particularly elevated cardiovascular risk with relative risk of 1.63 for vascular events versus placebo 5

Bleeding Risk in High-Risk Patients

Absolute Contraindications

• NSAIDs must be avoided in patients with platelet defects or thrombocytopenia due to dangerous synergistic effects on bleeding risk 6, 5

• When combined with anticoagulants, NSAIDs increase gastrointestinal bleeding risk 3-6 fold 5

• The antiplatelet effects combined with compromised hemostasis create unacceptable bleeding risk 6

Safer Alternatives

• Acetaminophen is the preferred analgesic for patients with thrombocytopenia, stroke history, or those requiring anticoagulation 6, 3

• Topical NSAIDs (diclofenac gel or patch) have minimal systemic absorption and may be used when oral NSAIDs are contraindicated 5

• If NSAIDs are absolutely necessary with anticoagulation, initiate proton pump inhibitor prophylaxis and monitor INR closely, anticipating 15% increases 5

Clinical Algorithm for NSAID Use with Aneurysms

For unruptured intracranial or abdominal aortic aneurysms:

• Consider NSAIDs acceptable if no contraindications exist (no anticoagulation, normal platelet function, no cardiovascular disease) 1, 2
• Monitor blood pressure and cardiovascular status given NSAID-associated risks 5

For aneurysmal subarachnoid hemorrhage:

• Avoid NSAIDs with strong antiplatelet effects (ketoprofen, ibuprofen, naproxen) for 5 elimination half-lives before surgery 5, 3
• Use acetaminophen for perioperative pain control 3
• Consider NSAIDs postoperatively only after hemostasis is secure, weighing anti-inflammatory benefits against bleeding risk 4

For patients with aneurysms requiring anticoagulation:

• Avoid oral NSAIDs entirely 5, 6
• Use acetaminophen as first-line analgesic 6
• Consider topical NSAIDs if pain control inadequate 5, 6

Key Pitfalls to Avoid

• Do not assume all NSAIDs are equivalent—COX-2 selective agents have different cardiovascular and bleeding profiles than nonselective NSAIDs 5, 1

• Do not overlook that aspirin's antiplatelet effects last 8-12 days (platelet lifespan), requiring longer preoperative discontinuation than other NSAIDs 5

• Do not combine NSAIDs with anticoagulants without GI prophylaxis and close INR monitoring 5

• Do not use NSAIDs in patients with congestive heart failure or uncontrolled hypertension 5