What is the best alternative antihypertensive agent for a patient with gout, hyperuricemia, and impaired renal function, currently on bendroflumethiazide (Thiazide diuretic)?

Management of Hypertension in a Patient with Hyperuricemia and Gout

The most appropriate antihypertensive agent to replace bendroflumethiazide in this patient with gout, hyperuricemia, and declining renal function is losartan, an angiotensin receptor blocker (ARB).

Rationale for Medication Change

• Thiazide diuretics like bendroflumethiazide are known to increase serum uric acid levels and can precipitate gout attacks, making them unsuitable for patients with hyperuricemia and gout 1
• The patient's current bendroflumethiazide is likely contributing to the elevated urate level of 0.45 mmol/L (above the target range of 0.16-0.42 mmol/L) 2
• The patient has already experienced adverse reactions to both allopurinol (pruritus) and probenecid (hair loss), limiting urate-lowering therapy options 3
• The patient's renal function is declining (eGFR 60, previously 71-76), which is another reason to avoid thiazide diuretics 2

Recommended Alternative: ARB (Losartan)

• When gout occurs in a patient receiving thiazide diuretics, the EULAR guidelines specifically recommend substituting the diuretic if possible, and for hypertension, consider losartan or calcium channel blockers 1
• Losartan has unique uricosuric properties among ARBs, which can help lower serum uric acid levels while effectively controlling blood pressure 1
• ARBs are recommended as first-line agents for hypertension in patients with chronic kidney disease, particularly those with albuminuria 1
• ARBs provide cardiovascular protection and are suitable for patients with diabetes (the patient has T2DM with an HbA1c of 53 mmol/mol) 1

Dosing and Monitoring

• Start losartan at a low dose (25-50 mg daily) and titrate based on blood pressure response 1
• Monitor renal function and serum potassium within 1-2 weeks of initiation 1
• Target blood pressure should be <140/90 mmHg in this patient with diabetes and chronic kidney disease 1
• Continue to monitor uric acid levels to assess the impact of medication change 1

Alternative Options if ARBs are Contraindicated

• Calcium channel blockers (particularly amlodipine or felodipine) are suitable alternatives that do not adversely affect uric acid metabolism 1
• Loop diuretics may be considered if diuretic therapy is essential for volume control, as they have less impact on uric acid levels than thiazides, particularly at lower doses 4
• Avoid beta-blockers if possible, as traditional beta-blockers may worsen glucose tolerance 1

Management of Concurrent Hyperuricemia

• Despite changing the antihypertensive medication, the patient may still require urate-lowering therapy 1
• Given the patient's previous adverse reactions to allopurinol and probenecid, febuxostat could be considered as an alternative urate-lowering agent, particularly suitable for patients with renal impairment 1, 5
• Target serum uric acid level should be <6 mg/dL (0.36 mmol/L) 1, 5

Potential Pitfalls and Cautions

• Avoid combining ACE inhibitors with ARBs due to increased risk of renal dysfunction 1
• Monitor for hypotension, especially when initiating therapy, as the patient is elderly (74 years) 1
• Be aware that the patient's leg swelling may be multifactorial (chronic venous insufficiency, possible heart failure component) and may not completely resolve with antihypertensive medication change 1
• The declining eGFR requires close monitoring of renal function after any medication change 1