What is the next antihypertensive agent to consider in a patient with uncontrolled hypertension, currently taking Cardizem (Diltiazem) 240mg ER daily, Torsemide (Torsemide) 20mg daily, and Hydralazine (Hydralazine) 100mg TID, with no ACE (Angiotensin-Converting Enzyme) inhibitors or ARBs (Angiotensin Receptor Blockers) allowed?

Next Antihypertensive Agent for Uncontrolled Hypertension Without ACE/ARBs

Spironolactone should be added as the next antihypertensive agent for this patient with uncontrolled hypertension who cannot take ACE inhibitors or ARBs. 1

Current Medication Analysis

The patient is currently on:

• Diltiazem (Cardizem) 240mg ER daily - a non-dihydropyridine calcium channel blocker
• Torsemide 20mg daily - a loop diuretic
• Hydralazine 100mg TID - a direct vasodilator

Despite this three-drug regimen, the patient remains hypertensive with systolic blood pressure in the 170s, indicating resistant hypertension.

Recommended Next Agent

Spironolactone as Fourth-Line Therapy

Spironolactone is the most appropriate next agent for several reasons:

• The 2024 ESC guidelines specifically recommend spironolactone as the preferred fourth-line agent for resistant hypertension 1
• The 2018 AHA/ACC guidelines list aldosterone antagonists (spironolactone or eplerenone) as preferred agents in resistant hypertension 1
• The 2020 International Society of Hypertension guidelines recommend adding spironolactone after a three-drug regimen fails to control blood pressure 1

Dosing Recommendation

• Start with spironolactone 25mg once daily
• Monitor renal function and serum electrolytes at 1 and 4 weeks after initiation
• Consider dose up-titration to 50mg daily after 4-8 weeks if needed and if no adverse effects occur 1

Alternative Options (If Spironolactone Is Not Tolerated)

If spironolactone causes adverse effects or is contraindicated, consider these alternatives in order of preference:

1. Eplerenone (25-50mg daily) - another mineralocorticoid receptor antagonist with less risk of gynecomastia 1

2. Beta-blocker - preferably a cardioselective agent such as metoprolol succinate or bisoprolol 1

   • Avoid non-cardioselective beta-blockers due to potential adverse effects 2

3. Alpha-1 blocker - such as doxazosin (1-16mg daily) 1

4. Potassium-sparing diuretics - amiloride if spironolactone and eplerenone are not tolerated 1

Monitoring Recommendations

When starting spironolactone:

• Check baseline renal function and serum electrolytes
• Recheck at 1 week and 4 weeks after initiation
• Monitor for hyperkalemia, especially if potassium rises above 5.5 mmol/L
• Watch for worsening renal function (creatinine >220 μmol/L or 2.5 mg/dL) 1

Rationale for Recommendation

Spironolactone has demonstrated superior efficacy in resistant hypertension compared to other fourth-line agents. The patient's current regimen includes a calcium channel blocker, loop diuretic, and vasodilator, but lacks a medication targeting the renin-angiotensin-aldosterone system. Since ACE inhibitors and ARBs are not allowed, an aldosterone antagonist provides an alternative approach to blocking this system.

Common Pitfalls to Avoid

• Hyperkalemia risk: Monitor potassium levels closely, especially if the patient has any degree of renal dysfunction
• Gynecomastia: More common with spironolactone than eplerenone; consider switching to eplerenone if this occurs
• Drug interactions: Be aware of potential interactions with the patient's existing medications
• Inadequate dosing: Ensure the patient is on maximally tolerated doses of current medications before adding a fourth agent

By adding spironolactone to the current regimen of diltiazem, torsemide, and hydralazine, you have the best chance of achieving blood pressure control in this patient who cannot take ACE inhibitors or ARBs.