Combination Therapy with Lisinopril and Spironolactone

Introduction to Combination Therapy

The American College of Cardiology recommends that lisinopril and spironolactone can be used together but require careful monitoring due to the significant risk of hyperkalemia, especially in patients with renal dysfunction, diabetes, or advanced age 1
The risk of hyperkalemia increases progressively when serum creatinine is >1.6 mg/dL, and higher doses of ACE inhibitors (lisinopril ≥10 mg daily) significantly increase hyperkalemia risk 1

Patients with baseline serum potassium >5.0 mEq/L, eGFR <30 mL/min/1.73 m², or concomitant use of other potassium-sparing medications are at higher risk of hyperkalemia 1, 2, 3
Elderly patients (≥70 years) and those with mild-to-moderate renal dysfunction (eGFR 30-49 mL/min/1.73 m²) require careful monitoring 1
Patients at risk for dehydration, taking NSAIDs, or with a history of severe hyperkalemia should be closely monitored 1

For patients with heart failure and normal renal function, start spironolactone at 12.5 mg daily and use lower doses of lisinopril (<10 mg daily) 1, 4
For patients with eGFR 30-49 mL/min/1.73 m², consider every-other-day dosing of spironolactone and reduce lisinopril dose 1
Discontinue potassium supplements when starting spironolactone, and check potassium and renal function within 2-3 days after initiation, again at 7 days, and monthly for the first 3 months 1, 2

If potassium exceeds 5.5 mEq/L, reduce dose or discontinue spironolactone, and if renal function worsens, evaluate entire medication regimen and consider stopping spironolactone 1
Instruct patients to temporarily stop spironolactone during episodes of diarrhea, dehydration, or when loop diuretic therapy is interrupted 1

The combination of lisinopril and spironolactone is particularly beneficial in heart failure with reduced ejection fraction (HFrEF) and resistant hypertension, where spironolactone is a preferred add-on agent when BP remains uncontrolled on multiple medications 5

Counsel patients to avoid high-potassium foods, and avoid triple combination of ACE inhibitor, ARB, and aldosterone antagonist 1
Avoid NSAIDs in patients on this combination, and consider using eplerenone instead of spironolactone in patients experiencing side effects 1