Does losartan (angiotensin II receptor antagonist) increase the risk of gout flares in patients with hypertension and gout?

Losartan and Gout Flares in Hypertensive Patients

Losartan does not increase gout flares but actually has uricosuric properties that can help reduce serum uric acid levels and potentially decrease the risk of gout attacks in patients with hypertension and gout. 1

Mechanism of Action and Effects on Uric Acid

Losartan stands apart from other antihypertensive medications due to its unique dual benefits:

• Uricosuric effect: Losartan increases urinary excretion of uric acid, leading to lower serum uric acid levels 1, 2
• Magnitude of effect: Studies show losartan can decrease serum uric acid levels from 538 ± 26 to 491 ± 20 μmol/L (p < 0.01) 2
• Sustained effect: The uricosuric effect of losartan persists with continued use, though it may stabilize once a new lower steady state of serum uric acid is reached 2

Clinical Recommendations for Hypertensive Patients with Gout

The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines specifically recommend:

• Preferred antihypertensive: Losartan is conditionally recommended as a preferred antihypertensive agent for patients with gout, regardless of disease activity 1
• Diuretic alternatives: When feasible, switching from hydrochlorothiazide (a known gout risk factor) to losartan is recommended for hypertensive patients with gout 1
• Rationale: Thiazide diuretics increase gout risk (OR = 1.72,95% CI: 1.67-1.76) through reduced renal uric acid excretion, while losartan has the opposite effect 1, 3

Dosing Considerations

• Standard dosing: Losartan 50 mg once daily is effective for lowering serum uric acid 2
• Increased dosing: Increasing to 50 mg twice daily does not appear to provide additional uric acid-lowering benefits compared to once-daily dosing 2
• Combination therapy: Losartan can be used in combination with anti-hyperuricemic agents (like allopurinol or benzbromarone) for enhanced uric acid reduction in patients with both hypertension and gout 4

Special Populations and Considerations

• Age effects: Losartan's urate-lowering effect may be more pronounced in adults under 60 years of age compared to older adults 5
• Safety profile: Losartan has been shown to be safe in patients with thiazide-induced hyperuricemia, without increasing the risk of acute urate nephropathy 6
• Unique among ARBs: While other angiotensin II receptor blockers (ARBs) like irbesartan do not demonstrate urate-lowering effects, losartan consistently shows this beneficial property 2, 7

Clinical Approach for Hypertensive Patients with Gout

1. For patients already on thiazide diuretics: Consider switching to losartan when clinically appropriate 1, 3
2. For patients starting antihypertensive therapy: Consider losartan as a first-line agent if they have hyperuricemia or gout 1
3. For difficult-to-control cases: Losartan can be used in combination with traditional urate-lowering therapies for enhanced effect 4

Pitfalls and Caveats

• While losartan has uricosuric effects, it should not replace dedicated urate-lowering therapy in patients with established gout requiring such treatment
• The clinical value of losartan as a primary urate-lowering agent remains unclear, despite its demonstrated biochemical effects 1
• Medication adherence is important - evening doses may have lower compliance rates than morning doses, potentially affecting twice-daily regimens 2