What dose of spironolactone to add to a 28-year-old heart failure patient's regimen, currently on carvedilol and furosemide, after discontinuing Entresto (sacubitril/valsartan) due to angioedema?

Spironolactone Dosing in Heart Failure After Entresto Discontinuation

Start spironolactone at 25 mg once daily in the morning, as this 28-year-old patient with NYHA class III/IV symptoms on carvedilol and furosemide meets criteria for mineralocorticoid receptor antagonist therapy. 1

Initial Dosing Strategy

• Begin with 25 mg once daily taken in the morning to minimize nighttime diuresis and sleep disruption 2
• This starting dose is recommended for patients already on ACE inhibitor/ARB (or in this case, after Entresto discontinuation) plus beta-blocker and diuretic therapy 1, 3
• The 25 mg dose provides effective aldosterone blockade while minimizing hyperkalemia risk, particularly in younger patients 4

Titration Protocol

• Target dose is 50 mg once daily, which should be achieved if tolerated after monitoring potassium and renal function 1, 2
• Increase to 50 mg daily only after checking serum potassium and creatinine at 1-2 weeks post-initiation 1
• If hyperkalemia develops (K+ >5.5 mEq/L), reduce back to 12.5-25 mg daily rather than discontinuing entirely 4

Critical Monitoring Requirements

Check potassium and creatinine within 1 week of initiation and again at 12 weeks, as this patient is on carvedilol which accelerates potassium elevation when combined with spironolactone 5

• Hyperkalemia risk is 13% at 25 mg dose and 20% at 50 mg dose when combined with ACE inhibitors/ARBs 4
• The combination of carvedilol + spironolactone + furosemide increases hyperkalemia risk to 11.9% even at low spironolactone doses 5
• Monitor for gynecomastia, particularly relevant in this young male patient 2

Special Considerations for This Patient

Since Entresto was discontinued due to angioedema, you must substitute an ACE inhibitor or ARB before or concurrent with spironolactone initiation 1, 3

• Spironolactone is indicated for NYHA class III-IV patients on maximal therapy with ACE inhibitor/ARB, beta-blocker, and diuretic 1, 3
• If ACE inhibitor is contraindicated due to the angioedema history, use an ARB (valsartan or candesartan) instead 3
• Do not use spironolactone without renin-angiotensin system blockade in this heart failure patient 1

Common Pitfalls to Avoid

• Never start at doses higher than 25 mg daily in patients on carvedilol, as beta-blockers potentiate hyperkalemia risk 5
• Avoid discontinuing spironolactone for mild hyperkalemia (K+ 5.5-5.9 mEq/L); instead reduce to 12.5 mg daily, as discontinuation increases mortality risk 2-4 fold 6
• Do not skip the 12-week blood chemistry check after final dose titration 1
• Lower doses (12.5-25 mg) are preferable to stopping treatment if target dose cannot be tolerated 6, 4

Dose Adjustments for Hyperkalemia

If K+ rises above 5.5 mEq/L:

• Reduce spironolactone to 12.5 mg daily (do not stop) 4
• Review ACE inhibitor/ARB dose and consider temporary reduction 4
• Ensure adequate diuresis with furosemide to promote potassium excretion 5
• Recheck potassium in 3-5 days after dose adjustment 1