What is the recommended use of Mineralocorticoid Receptor Antagonists (MRA)?

Recommended Use of Mineralocorticoid Receptor Antagonists (MRAs)

Mineralocorticoid receptor antagonists (MRAs) are strongly recommended for patients with heart failure with reduced ejection fraction (HFrEF) and NYHA class II-IV symptoms with LVEF ≤35%, resistant hypertension, and diabetic kidney disease with albuminuria, as they significantly reduce mortality and morbidity when added to standard therapy.

MRAs in Heart Failure with Reduced Ejection Fraction

Indications

• MRAs (spironolactone and eplerenone) are indicated for all symptomatic patients with HFrEF and LVEF ≤35% despite treatment with an ACE inhibitor/ARB and a beta-blocker 1
• Provides high economic value with significant mortality and hospitalization reduction 1, 2

Dosing and Administration

• Starting dose: 25 mg orally daily (spironolactone or eplerenone)
• Target dose: 50 mg orally daily after one month if tolerated 1, 2
• For patients with eGFR 31-49 mL/min/1.73 m², reduce dosing by half 1

Monitoring Requirements

• Check serum potassium and renal function:
  • Approximately 1 week after initiation
  • 4 weeks after initiation or dose change
  • Every 6 months once stable
  • More frequent testing during clinical instability 1, 2

Contraindications

• eGFR <30 mL/min/1.73 m²
• Serum potassium ≥5.0 mEq/L 1, 2

MRAs in Resistant Hypertension

• Indicated for patients not meeting blood pressure targets on three classes of antihypertensive medications, including a diuretic 1, 2
• Particularly effective when added to existing treatment with ACE inhibitor/ARB, thiazide-like diuretic, and dihydropyridine calcium channel blocker 1, 3
• Dose range for resistant hypertension: 25-50 mg/day of spironolactone 3
• Eplerenone is an appropriate alternative if spironolactone is not tolerated due to sexual side effects 3

MRAs in Diabetic Kidney Disease

• Recommended for patients with type 2 diabetes, eGFR ≥25 mL/min/1.73 m², normal serum potassium, and albuminuria (≥30 mg/g) despite maximum tolerated dose of RAS inhibitor 1, 2
• Nonsteroidal MRAs (like finerenone) can be added to a RAS inhibitor and an SGLT2i for treatment of T2D and CKD 1
• Reduces albuminuria and provides cardiovascular benefits 1, 2

Safety Considerations and Management of Adverse Effects

Hyperkalemia Risk

• MRAs increase risk of hyperkalemia, especially when combined with ACE inhibitors or ARBs 2, 4
• For K+ >5.5 mmol/L, halve the dose and monitor closely
• For K+ >6.0 mmol/L or if serum potassium cannot be maintained <5.5 mEq/L, discontinue MRA 1, 2

Renal Function

• Monitor for acute deterioration of renal function, especially during initial treatment period 4
• Discontinue if creatinine increases by more than 30% 2

Sex-Related Adverse Events

• More common with spironolactone (due to its non-selective binding to progesterone and androgen receptors)
• Consider switching to eplerenone if these occur, as it has fewer progestational and antiandrogenic effects 3, 4, 5

Practical Considerations

• When initiating MRAs in patients at risk for hypovolemia, consider decreasing thiazide or loop diuretic dosages first 1
• Avoid combination therapy with MRAs and both ACE inhibitors and ARBs simultaneously 2
• For patients with heart failure, MRAs can be safely initiated before hospital discharge if patients are clinically stabilized 1
• In resistant hypertension, combining spironolactone with adequate doses of a thiazide diuretic maximizes efficacy and reduces hyperkalemia risk 3

Emerging Developments

• Newer nonsteroidal MRAs (like finerenone) show promise with potentially improved selectivity and fewer adverse effects 6, 5
• Finerenone has shown benefits in patients with HF with preserved ejection fraction and in patients with diabetes and albuminuric chronic kidney disease 6

By following these evidence-based recommendations and monitoring protocols, MRAs can be safely and effectively used to reduce mortality, morbidity, and disease progression in multiple cardiovascular and renal conditions.