Is aspirin (acetylsalicylic acid) or eplerenone more likely to precipitate gout attacks?

Aspirin vs Eplerenone and Gout Risk

Low-dose aspirin is directly connected to precipitating gout attacks, while eplerenone has no established connection to triggering gout flares. 1, 2

Aspirin and Gout: The Evidence

Aspirin increases gout attack risk but should NOT be discontinued when used for cardiovascular indications. The 2020 American College of Rheumatology guidelines explicitly recommend against stopping low-dose aspirin in patients taking it for appropriate cardiovascular indications, regardless of gout disease activity. 1

Mechanism and Clinical Impact

• Low-dose aspirin (≤325 mg/day) elevates serum uric acid levels and directly triggers gout attacks. 3, 4
• Use of aspirin ≤325 mg/day on two consecutive days increases the risk of recurrent gout attacks by 81% (OR=1.81,95% CI 1.30-2.51). 2
• The effect is paradoxically stronger at lower doses: aspirin ≤100 mg/day shows an even higher risk (OR=1.91,95% CI 1.32-2.85). 2
• This increased risk persists across all patient subgroups including those with renal insufficiency. 2

Critical Management Strategy

Concomitant use of allopurinol completely nullifies the detrimental effect of aspirin on gout attacks. 2 This is the key clinical takeaway:

• Continue aspirin for cardiovascular protection (the benefits outweigh gout risks). 1
• Initiate or optimize urate-lowering therapy (allopurinol or febuxostat) to target serum uric acid <6 mg/dL. 2
• Monitor serum urate levels regularly and adjust urate-lowering therapy doses accordingly. 2

Common Pitfall to Avoid

Do not discontinue aspirin in patients with cardiovascular indications simply because they have gout. The ACR guidelines recognize that "there are few practical alternatives to low-dose aspirin" for cardiovascular protection, making discontinuation inappropriate despite the increased gout risk. 1

Eplerenone and Gout: No Direct Connection

Eplerenone is not associated with precipitating gout attacks. The 2024 multispecialty practice recommendations note that steroidal mineralocorticoid receptor antagonists (spironolactone and eplerenone) are associated with hyperkalemia risk, but make no mention of gout or hyperuricemia. 1

Key Distinctions

• Thiazide and loop diuretics (like hydrochlorothiazide) are the diuretic classes that precipitate gout by reducing uric acid excretion. 1, 3, 5
• Eplerenone, as a mineralocorticoid receptor antagonist, works through a different mechanism (blocking sodium reabsorption through the mineralocorticoid receptor) and does not share the hyperuricemic effects of thiazide/loop diuretics. 1
• The primary concern with eplerenone is hyperkalemia, not gout. 1

Clinical Algorithm for Medication Management in Gout

When evaluating medications in gout patients:

1. Identify true culprits: Thiazide diuretics, loop diuretics, low-dose aspirin, cyclosporine, tacrolimus, and niacin increase gout risk. 3, 4

2. For aspirin users with gout:

   • Continue aspirin if prescribed for cardiovascular indications. 1
   • Initiate allopurinol or febuxostat to achieve serum uric acid <6 mg/dL. 2
   • Monitor serum urate levels and adjust urate-lowering therapy accordingly. 2

3. For diuretic users with gout:

   • Switch hydrochlorothiazide to losartan (which has uricosuric effects). 1, 5
   • Consider calcium channel blockers as alternatives. 5

4. For eplerenone users: No gout-specific changes needed; monitor potassium instead. 1