What is an alternative to spironolactone (Mineralocorticoid Receptor Antagonist) and finerenone (Mineralocorticoid Receptor Antagonist) for managing heart failure or resistant hypertension?

Alternatives to Spironolactone and Finerenone for Managing Resistant Hypertension

When spironolactone and finerenone are not available, eplerenone is the preferred alternative mineralocorticoid receptor antagonist (MRA) for managing resistant hypertension. 1

First-Line Alternative: Eplerenone

Eplerenone is a selective MRA that offers several advantages over spironolactone:

• Efficacy: While slightly less potent than spironolactone, eplerenone is effective for resistant hypertension management 2
• Dosing: Start at 25mg once daily and titrate to 50mg once daily, preferably within 4 weeks 3
• Reduced side effects: Fewer anti-androgenic side effects (no gynecomastia, sexual dysfunction, or menstrual irregularities) due to its selectivity for the mineralocorticoid receptor 4, 3
• Administration: Due to its shorter half-life compared with spironolactone, eplerenone should be administered twice daily for optimal effect 4

Second-Line Alternatives

If eplerenone is unavailable or contraindicated, consider:

1. Amiloride

• Potassium-sparing diuretic that works through a different mechanism (epithelial sodium channel blockade)
• Often prescribed for essential hypertension as a fixed-dose combination with hydrochlorothiazide 5
• Particularly useful when MRAs cannot be used

2. Thiazide-like Diuretics

• Chlorthalidone: More effective than hydrochlorothiazide with an additional SBP reduction of 7-8 mmHg 4
• Indapamide: Alternative thiazide-like diuretic with strong evidence for reducing cardiovascular outcomes 4, 1

3. Other Agents Based on Patient Characteristics

For patients with elevated heart rate (>80 bpm):

• Beta-blockers: Consider if no contraindications exist 4
• Central α-2 agonists: Such as transdermal clonidine or guanfacine (avoid clonidine tablets due to risk of rebound hypertension) 4

For patients with normal heart rate:

• Alpha-blockers: Such as doxazosin 1
• Vasodilators: Such as hydralazine 1

Monitoring Recommendations

1. Electrolytes: Monitor serum potassium, sodium, and magnesium 1-2 weeks after initiation and every 3-6 months thereafter (more frequently in patients with reduced kidney function) 1

2. Kidney function: Check serum creatinine and eGFR before starting treatment, 1-2 weeks after initiation, and periodically thereafter 1

3. Blood pressure: Use ambulatory or home BP monitoring to confirm diagnosis and monitor treatment response 1

Important Considerations and Pitfalls

• Hyperkalemia risk: All potassium-sparing agents increase the risk of hyperkalemia, especially in patients with CKD (eGFR <45 mL/min/1.73m²), concomitant use of ACE inhibitors or ARBs, or advanced age 1

• Optimize diuretic therapy: Before adding alternative agents, ensure optimal diuretic therapy by substituting chlorthalidone or indapamide for hydrochlorothiazide 1

• Medication adherence: Address barriers to adherence such as cost, side effects, and dosing complexity; consider single-pill combinations when possible 1

• Secondary causes: Rule out secondary causes of resistant hypertension, including primary aldosteronism, obstructive sleep apnea, and renal artery stenosis 1

• Avoid inappropriate combinations: Do not combine ACE inhibitors with ARBs due to increased risk of adverse events without additional benefits 4

Algorithm for Management

1. Confirm true resistant hypertension using ambulatory or home BP monitoring
2. Optimize current regimen: Ensure optimal doses of RAS blocker (ACE inhibitor or ARB), long-acting calcium channel blocker, and appropriate diuretic
3. Add eplerenone as the fourth agent if spironolactone and finerenone are unavailable
4. If eplerenone is ineffective or unavailable, choose from:
   • Amiloride (especially if concerned about hyperkalemia)
   • Enhanced diuretic therapy with chlorthalidone or indapamide
   • Additional agents based on heart rate and comorbidities

By following this evidence-based approach, resistant hypertension can be effectively managed even when first-line MRAs like spironolactone and finerenone are unavailable.