Continue Lisinopril and Add an SGLT2 Inhibitor
The optimal approach is to restart lisinopril at a lower dose (or continue if not yet discontinued) while simultaneously adding an SGLT2 inhibitor, which will help lower potassium levels and enable continuation of guideline-directed medical therapy (GDMT) for this patient's HFrEF. 1
Rationale for Maintaining ACE Inhibitor Therapy
Your patient has a potassium of 5.6 mEq/L—this is moderate hyperkalemia, not severe. The most recent 2025 guideline evidence explicitly addresses this exact clinical scenario and demonstrates that discontinuing RAAS inhibitors for hyperkalemia leads to worse cardiovascular outcomes and increased mortality 1. In the DIAMOND trial, over 80% of patients did not develop recurrent hyperkalemia when rechallenged with RAAS inhibitors, even without potassium binders 1.
The lisinopril dose is only 10 mg daily—this is a low dose that provides suboptimal neurohormonal blockade for HFrEF. Older guidelines noted that higher doses of ACE inhibitors (≥10 mg lisinopril) increase hyperkalemia risk 2, but this patient is at the threshold, not above it.
Primary Strategy: Add SGLT2 Inhibitor
SGLT2 inhibitors reduce the risk of serious hyperkalemia by 16% (HR 0.84; 95% CI 0.76-0.93) in patients taking RAAS inhibitors and MRAs 1. This effect occurs through:
- Enhanced natriuresis and kaliuresis
- Reduced need for loop diuretic doses
- Improved volume status without excessive diuretic use
The 2025 AJKD guideline specifically recommends adding an SGLT2 inhibitor together with reintroduction of RAAS inhibitors as the preferred strategy for managing hyperkalemia in HFrEF with CKD 1.
Secondary Strategies if SGLT2 Inhibitor Insufficient
Consider Potassium Binders
If potassium remains >5.5 mEq/L despite SGLT2 inhibitor:
- Patiromer (DIAMOND trial: HR 0.63 for hyperkalemia >5.5 mEq/L vs placebo) 1, 3
- Sodium zirconium cyclosilicate (SZC) 4, 3, 5
These newer binders are far superior to sodium polystyrene sulfonate, which has serious adverse effects and limited chronic efficacy 4, 6.
Alternative: Switch to Sacubitril/Valsartan
Sacubitril/valsartan causes 27% less severe hyperkalemia compared to enalapril (HR 1.37 for enalapril vs sacubitril/valsartan) 1. This is a reasonable alternative if SGLT2 inhibitor plus ACE inhibitor strategy fails.
What NOT to Do
Do not simply increase torsemide dose 1. The patient appears euvolemic based on the clinical scenario (no volume overload mentioned). Diuretics should be titrated to maintain euvolemia, not used primarily for potassium management 7, 2. Excessive diuresis causes:
Do not add spironolactone with potassium at 5.6 mEq/L. Guidelines explicitly state MRAs should not be initiated when potassium >5.0 mEq/L 2, 8, 2. The creatinine threshold for MRA initiation is also concerning (should be ≤2.5 mg/dL in men, and eGFR >30 mL/min/1.73m²) 2, 8.
Monitoring Protocol
After restarting/continuing lisinopril and adding SGLT2 inhibitor:
- Check potassium and creatinine in 2-3 days, then at 7 days 9, 2
- Monthly monitoring for first 3 months, then every 3 months 2
- If potassium rises to >5.5 mEq/L: add potassium binder rather than stopping ACE inhibitor 1, 5
- If potassium >6.0 mEq/L or symptomatic: temporarily hold ACE inhibitor, treat acutely, then rechallenge at lower dose with potassium binder 4, 5
Additional Considerations
Review and eliminate reversible factors 5:
- Discontinue potassium supplements if prescribed
- Avoid NSAIDs 9, 10
- Counsel on avoiding high-potassium foods and salt substitutes 2, 10
- Check for constipation (reduces GI potassium excretion) 5
- Assess for metabolic acidosis 4, 5
The magnesium level of 2.5 mg/dL is normal and does not require intervention.
The overarching principle: GDMT withdrawal is associated with worse outcomes than tolerating mild-to-moderate hyperkalemia with appropriate management strategies 1, 4, 5. The goal is maintaining optimal neurohormonal blockade while managing potassium through adjunctive therapies, not by sacrificing life-saving medications.