Does Losartan Lower Uric Acid Levels?
Yes, losartan uniquely lowers serum uric acid levels through its uricosuric properties, increasing urinary uric acid excretion by approximately 25% and reducing serum uric acid by 20-47 μmol/L, making it the preferred antihypertensive agent for patients with hyperuricemia or gout. 1, 2, 3
Mechanism and Clinical Evidence
Losartan stands apart from other angiotensin II receptor blockers through its specific uricosuric action:
Losartan increases urinary uric acid excretion while simultaneously raising urine pH, which decreases dihydrogen urate (the primary risk factor for crystal formation), thereby lowering serum uric acid without increasing the risk of acute urate nephropathy 4
The uric acid-lowering effect is dose-dependent initially but reaches a plateau at 50 mg daily; increasing to 50 mg twice daily does not produce additional serum uric acid reduction 3
Losartan 50 mg daily decreased serum uric acid from 538 to 491 μmol/L (P < 0.01) in hypertensive patients with hyperuricemia and gout, representing approximately a 9% reduction 3
Comparison with Other ARBs
Losartan's uricosuric effect is unique among angiotensin receptor blockers:
Irbesartan has no effect on serum uric acid levels in direct comparison studies, despite similar blood pressure control 3, 5
Eprosartan does not increase uric acid excretion, though it may modestly reduce serum urate levels similar to losartan through blood pressure reduction alone 5
The uricosuric effect appears specific to losartan's molecular structure, not a class effect of ARBs 3, 5
Guideline-Based Recommendations
Major clinical guidelines specifically recommend losartan for patients with gout or hyperuricemia:
The EULAR guidelines recommend stopping diuretics when possible in gout patients and considering losartan for hypertension due to its modest uricosuric effects, though noting that long-term clinical value remains unclear 1
The American College of Cardiology recommends losartan as the preferred alternative to diuretics for patients at risk of gout, as it does not increase serum uric acid and may lower it 2
For patients with existing gout, switching from diuretics to losartan for hypertension management is specifically recommended 2
Clinical Application in Special Populations
Thiazide-induced hyperuricemia:
Losartan is particularly effective in reversing thiazide-induced hyperuricemia, with combination therapy (losartan + thiazide) showing 13.27% increase in urinary uric acid excretion versus 6.7% with losartan alone 6
Losartan safely increases uric acid excretion without causing acute urate nephropathy even in patients with thiazide-induced hyperuricemia (serum uric acid 7.0-12.0 mg/dL) 4
Heart failure patients:
High-dose losartan (150 mg) reduced serum uric acid by 0.27 mg/dL more than low-dose (50 mg) and reduced the incidence of hyperuricemia in the HEAAL trial 7
The cardiovascular benefits of losartan were not modified by baseline serum uric acid levels, indicating consistent efficacy across the hyperuricemia spectrum 7
Important Clinical Caveats
Timing and magnitude of effect:
The uricosuric effect of losartan appears to decrease over time as a new steady state of lower serum uric acid is reached, with maximal effects seen in the first week 3, 4
Urinary uric acid excretion increases significantly at 4 and 6 hours after the first dose, with sustained but less pronounced effects at days 7 and 21 4
Limitations in evidence:
No long-term randomized controlled trials exist evaluating losartan as monotherapy or in combination with other urate-lowering drugs specifically for gout treatment 1
The clinical role and cost-effectiveness of losartan as a urate-lowering agent remains undefined, though its dual benefit for hypertension and hyperuricemia makes it attractive for appropriate patients 1
Safety considerations:
Losartan does not increase the risk of acute urate nephropathy despite increasing urinary uric acid excretion, due to concurrent increases in urine pH that reduce dihydrogen urate formation 4
Standard monitoring for ARB therapy applies, including potassium levels and renal function, particularly in patients with chronic kidney disease 1