How to manage hyperkalemia in patients with heart failure and reduced ejection fraction (HFrEF)?

Management of Hyperkalemia in Heart Failure with Reduced Ejection Fraction (HFrEF)

For patients with HFrEF and hyperkalemia, adding SGLT2 inhibitors and potassium binders like patiromer are the most effective strategies to maintain guideline-directed medical therapy (GDMT) while controlling potassium levels. 1

Understanding Hyperkalemia in HFrEF

Hyperkalemia is a common complication in HFrEF patients, particularly those on renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs). The prevalence is notably higher in patients with comorbidities such as:

• Chronic kidney disease (CKD)
• Diabetes mellitus
• Advanced age

Hyperkalemia severity is typically classified as:

• Mild: >5.0 to <5.5 mEq/L
• Moderate: 5.5 to 6.0 mEq/L
• Severe: >6.0 mEq/L 1

Management Algorithm

1. Assessment and Initial Management

• Verify true hyperkalemia with repeat testing to rule out pseudohyperkalemia 2
• For potassium >5.5 mmol/L, consider immediate intervention
• For potassium 5.0-5.5 mmol/L, consider medication adjustments while maintaining GDMT

2. Medication Optimization Strategies

First-line approaches (maintain GDMT):

1. Add SGLT2 inhibitors - These reduce hyperkalemia risk while providing cardiovascular benefits 1

   • SGLT2 inhibitors have been shown to reduce the risk of serious hyperkalemia (hazard ratio 0.84; 95% CI 0.76-0.93) 1
   • They may also reduce the need for loop diuretic doses

2. Add potassium binders - Consider for patients with current or history of hyperkalemia 1, 3

   • Patiromer: In the DIAMOND trial, patiromer significantly reduced hyperkalemia rates compared to placebo (hazard ratio 0.63; 95% CI 0.45-0.87) 1, 3
   • Sodium zirconium cyclosilicate (SZC): Effective for rapid potassium lowering 4, 5
   • Dosing:
     • Patiromer: 8.4g once daily
     • SZC: 10g three times daily for 48 hours, then 5-10g daily for maintenance 2

3. Switch to sacubitril/valsartan - Associated with lower hyperkalemia risk compared to ACE inhibitors 1

   • Analysis from PARADIGM-HF showed lower rates of severe hyperkalemia with sacubitril/valsartan compared to enalapril (hazard ratio 1.37; 95% CI 1.06-1.76 for enalapril vs. sacubitril/valsartan) 1

Second-line approaches (if first-line fails):

1. Adjust diuretic therapy - Consider increasing loop diuretic dose if patient has signs of fluid retention 1

   • Note: Diuretics should be titrated primarily to maintain euvolemia, not just to manage potassium 1

2. Medication dose adjustment - For potassium 5.0-5.5 mmol/L, consider reducing doses of RAASi/MRAs rather than discontinuing 2

3. Careful rechallenge - In the DIAMOND trial, >80% of patients in the placebo group did not develop hyperkalemia despite RAASi uptitration 1

3. Monitoring Protocol

• Recheck potassium and renal function within 2-3 days after any medication adjustment 2
• Follow up again at 7 days 2
• Continue monitoring monthly for at least 3 months 2
• Any increase in ACE inhibitor/ARB dose should trigger a new cycle of monitoring 2

Special Considerations

Dietary Management

• Restrict dietary potassium intake to <2,000-3,000 mg daily 2
• Advise patients to avoid high-potassium foods and salt substitutes containing potassium 2

Renal Function Changes

• Changes in kidney function with HF management should be interpreted in context of decongestion and GDMT initiation/uptitration 1
• Worsening kidney function during successful decongestion may not reflect true tubular injury 1

Economic Impact

• Hyperkalemia generates substantial healthcare costs, especially in the first year of management 6
• Reduction or withdrawal of RAASi is necessary in approximately 70% of hyperkalemia episodes, potentially compromising outcomes 6

Common Pitfalls to Avoid

1. Discontinuing GDMT prematurely - Discontinuation of RAASi/MRAs is associated with poorer clinical outcomes 1

2. Ignoring mild hyperkalemia - Even mild elevations can progress and should be addressed proactively 2

3. Failing to consider pseudohyperkalemia - Always verify true hyperkalemia with repeat testing 2

4. Inadequate monitoring - Regular monitoring is essential, especially after medication adjustments 2

5. Focusing only on potassium levels - The goal is to optimize GDMT while managing hyperkalemia, not just normalize potassium at the expense of beneficial therapies 7

By implementing these strategies, clinicians can effectively manage hyperkalemia while maintaining life-saving GDMT in patients with HFrEF, ultimately improving morbidity and mortality outcomes.