What is the role of spironolactone in treating atrial fibrillation and heart failure?

Role of Spironolactone in Atrial Fibrillation and Heart Failure

Spironolactone is a second-line therapy that improves survival, reduces hospitalizations, and improves NYHA functional class in patients with moderate to severe heart failure (NYHA class III-IV), and may have a role in rate control for atrial fibrillation, particularly in patients with heart failure with preserved ejection fraction (HFpEF). 1

Role in Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Spironolactone is indicated as second-line therapy (after ACE inhibitors and beta-blockers) in patients with NYHA class III-IV heart failure 1
• The RALES study demonstrated that low-dose spironolactone increased survival, reduced hospital admissions, and improved NYHA class when added to standard therapy in severe heart failure 1
• Starting dose is 25 mg once daily or on alternate days, with a target dose of 25-50 mg once daily 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Spironolactone may be beneficial in selected HFpEF patients, particularly those with LVEF in the lower spectrum (41-49%) 1
• The TOPCAT trial showed a non-significant reduction in the composite of death and heart failure hospitalization, but did demonstrate a significant reduction in heart failure hospitalizations 1
• Post-hoc analyses suggest potential efficacy in appropriately selected patients with symptomatic HFpEF (LVEF ≥45%, elevated BNP level or HF admission within 1 year) 1
• Spironolactone improves cardiac structure and function in HFpEF patients, including reducing left atrial volume index, left ventricular mass index, and E/e' ratio 2

Role in Atrial Fibrillation

Rate Control in Atrial Fibrillation

• In patients with HFpEF and atrial fibrillation, beta-blockers or non-dihydropyridine calcium channel blockers are generally recommended as first-line therapy for heart rate control 1, 3
• Digoxin may have a special role in atrial fibrillation when rapid control of ventricular rate is needed, particularly when beta-blockers cannot be cautiously introduced and up-titrated 1
• The RATE-AF trial showed that digoxin may be preferable to beta-blockers in elderly patients with AF and heart failure symptoms, with fewer adverse events such as dizziness, lethargy, and hypotension 1

Prevention of Atrial Fibrillation

• Despite theoretical benefits through reduction of atrial fibrosis and inflammation, spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF 4
• The IMPRESS-AF trial found that spironolactone did not improve exercise capacity, E/e' ratio, or quality of life in patients with chronic atrial fibrillation and preserved ejection fraction 5
• However, smaller studies suggest spironolactone may improve atrial conduction and remodeling in patients with heart failure 6

Practical Use and Monitoring

Dosing and Administration

• Start at 25 mg once daily or on alternate days 1
• Target dose is 25-50 mg once daily 1
• Check blood chemistry at 1,4,8, and 12 weeks; 6,9, and 12 months; then 6-monthly thereafter 1

Monitoring for Adverse Effects

• Major concern is hyperkalemia (>6.0 mmol/L), though this was uncommon in the RALES study 1
• If potassium rises to between 5.5 and 6.0 mmol/L or creatinine rises to 2.5 mg/dL, reduce dose to 25 mg on alternate days and monitor blood chemistry closely 1
• If potassium rises above 6.0 mmol/L or creatinine rises significantly, seek specialist advice 1
• Male patients may develop breast discomfort and/or gynecomastia 1, 3

Drug Interactions and Precautions

• Use caution with ACE inhibitors, angiotensin receptor blockers, other potassium-sparing diuretics, and potassium supplements 1
• Avoid NSAIDs and "low salt" substitutes with high potassium content 1
• Temporarily stop spironolactone if diarrhea and/or vomiting occur and contact physician 1
• Contraindications include severe renal insufficiency and hyperkalemia 3

Patient Education

• Explain that treatment improves symptoms, prevents worsening of heart failure, and increases survival 1
• Symptom improvement typically occurs within a few weeks to a few months of starting treatment 1
• Advise patients to avoid over-the-counter NSAIDs 1
• Instruct patients to temporarily stop spironolactone if diarrhea or vomiting occurs and to contact their physician 1