Mineralocorticoid Receptor Antagonists in Clinical Practice

Introduction to Spironolactone and Finerenone

The American Heart Association recommends spironolactone as a cornerstone therapy in heart failure with reduced ejection fraction, proven to reduce morbidity and mortality when added to standard treatment with ACE inhibitors/ARBs and beta-blockers 3
The European Society of Cardiology provides spironolactone a Class IIa recommendation for resistant hypertension, acknowledging its effectiveness but noting the lack of dedicated cardiovascular outcome trials in primary hypertension populations 8

For resistant hypertension, spironolactone is the preferred fourth-line agent after optimizing a three-drug regimen, with evidence showing blood pressure reductions of approximately 21.7/8.5 mmHg 1, 2, 6, 7
The American College of Cardiology recommends spironolactone for resistant hypertension, with a blood pressure reduction of 24 and 10 mm Hg respectively when added to regimens of patients uncontrolled on at least 2 medications including an ACE inhibitor or ARB and diuretic 1

The American Heart Association recommends MRAs, including spironolactone, as part of combination therapy for heart failure with reduced ejection fraction, not monotherapy 7
The standard regimen includes an ACE inhibitor/ARB, beta-blocker, and MRA, with loop diuretics added as needed for volume management 7

Finerenone is specifically indicated for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m², normal serum potassium, and albuminuria (ACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy, representing a major advancement over spironolactone in this population 4, 3
Finerenone should be started at 20 mg daily for eGFR >60 mL/min/1.73 m² and 10 mg for eGFR 25-60 mL/min/1.73 m², with uptitration to 20 mg if tolerated 4

Finerenone's nonsteroidal structure and higher mineralocorticoid receptor selectivity eliminate the hormonal side effects that limit spironolactone use, particularly gynecomastia and sexual dysfunction in men 1, 2
Spironolactone's most common adverse effect is breast tenderness with or without breast enlargement, particularly in men, due to its non-selective receptor binding 1, 2

Both agents increase hyperkalemia risk, particularly in older patients, those with diabetes, CKD, or concurrent use of ACE inhibitors/ARBs/NSAIDs, requiring identical vigilance in potassium monitoring regardless of which agent is chosen 1, 2, 4
For finerenone, if potassium increases to >5.5 mmol/l, the drug should be withheld and can be restarted at 10 mg daily when potassium is ≤5.0 mmol/l 4

Choose spironolactone for resistant hypertension (after optimizing three-drug regimen) and HFrEF; choose finerenone for patients with type 2 diabetes and CKD with albuminuria despite RAS inhibitor therapy 4, 6, 7
For resistant hypertension: Start spironolactone 25 mg daily if potassium <4.5 mEq/L and eGFR >45 mL/min/1.73m², increase to 50 mg if needed 6
For diabetic CKD: Add finerenone to standard care if ACR ≥30 mg/g, eGFR ≥25 mL/min/1.73 m², and potassium ≤5.0 mmol/L 4

The most critical error is failing to monitor potassium adequately with either agent, particularly in patients on concurrent RAS inhibitors, which dramatically increases hyperkalemia risk 1, 2, 4
Do not combine spironolactone or finerenone with both an ACE inhibitor AND an ARB, as this triple combination significantly increases hyperkalemia and AKI risk 4