Mechanism of Losartan in Gout Suppression
Losartan uniquely lowers serum uric acid through direct uricosuric action by increasing urinary uric acid excretion by approximately 25%, making it the preferred antihypertensive agent for patients with both hypertension and gout. 1
Molecular Mechanism of Action
Losartan's uricosuric effect operates through enhanced renal tubular secretion of uric acid, directly increasing urinary uric acid excretion while simultaneously reducing serum uric acid levels by 20-47 μmol/L. 1 This mechanism is distinct from other angiotensin II receptor blockers (ARBs), as losartan is the only ARB that consistently demonstrates statistically significant reductions in serum uric acid levels across multiple studies. 2
The drug achieves this dual benefit by:
- Increasing renal uric acid clearance through enhanced tubular secretion 3
- Reducing serum uric acid concentrations by approximately 47 μmol/L (from 538 to 491 μmol/L) at the 50 mg daily dose 3
- Maintaining this effect without requiring dose escalation beyond 50 mg daily, as higher doses (50 mg twice daily) do not produce additional uric acid reduction 3
Clinical Evidence and Specificity
The uricosuric property is unique to losartan among ARBs—irbesartan, for example, shows no effect on serum uric acid levels in head-to-head comparisons. 3 This specificity makes losartan particularly valuable, as the American College of Rheumatology guidelines recognize it for off-label use as uricosuric therapy. 4
When combined with traditional anti-hyperuricemic agents (benzbromarone or allopurinol), losartan provides additional serum uric acid reduction through increased uric acid excretion, though the additional hypouricemic effect may be modest. 5
Guideline-Based Recommendations
The European League Against Rheumatism (EULAR) specifically recommends stopping diuretics when possible in gout patients and considering losartan for hypertension due to its modest uricosuric effects. 1 The American College of Cardiology recommends losartan as a preferred alternative to diuretics for patients at risk of gout, as it does not increase serum uric acid levels and provides modest uricosuric benefits. 1
For optimal cardiovascular and urate-lowering benefits, the target dose is 100 mg once daily, though the uricosuric effect may not substantially increase beyond 50 mg daily. 1
Important Clinical Caveats
- The uricosuric effect appears to decrease with time when a new steady state of lower serum uric acid is reached 3
- No long-term randomized controlled trials exist evaluating losartan as monotherapy or in combination with other urate-lowering drugs specifically for gout treatment, and the clinical role and cost-effectiveness as a urate-lowering agent remains undefined 1
- Standard ARB monitoring applies, including potassium levels and renal function, particularly in patients with chronic kidney disease 1
Practical Application for Hypertensive Gout Patients
For patients with both hypertension and gout, switching from diuretics (especially thiazide or loop diuretics) to losartan addresses both conditions simultaneously by lowering blood pressure while reducing serum uric acid levels. 1 The American College of Rheumatology conditionally recommends switching hydrochlorothiazide to alternative antihypertensives in gout patients, regardless of disease activity. 1