REALIZE-K: Potassium Binder Boosts MRA Use in Hyperkalemic HFrEF Patients

 Sodium zirconium cyclosilicate (SZC) enables the safe use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with reduced ejection fraction (HFrEF) at risk for hyperkalemia.

At 6 months, 71% of SZC-treated patients maintained normokalemia on spironolactone ≥ 25 mg/daily without rescue therapy compared to 36% in the placebo group (P < 0.001).

The study findings were presented at the American Heart Association 2024 Scientific Sessions.

Hyperkalemia risk is a primary reason for the down-titration or discontinuation of MRAs in real-world HFrEF management.

Adverse events, including heart failure and edema, were slightly higher in the SZC group than the placebo group.

A post-hoc analysis suggested these differences were more pronounced in patients with very high NT-proBNP levels at baseline.

The trial builds on findings from the DIAMOND trial, which showed similar benefits with the potassium binder patiromer.

However, DIAMOND did not fully explore how potassium binders optimize individual HFrEF therapies.

Discussant comments emphasized cautious use of potassium binders due to their sodium load, especially with SZC.

Each 5-gram packet of SZC contains 400 mg of sodium, raising concerns about heart failure hospitalizations.

Another concern is polypharmacy, as potassium binders require spacing other medications 2 hours apart.

REALIZE-K trial enrolled patients with symptomatic NYHA class II-IV HF and LVEF ≤ 40% from eight countries.

Patients were either hyperkalemic or at risk due to age or chronic kidney disease.

SZC was used during a run-in period to normalize potassium before randomizing patients to SZC or placebo.

At 6 months, 84.8% of SZC-treated patients maintained normokalemia compared to 50.9% in the placebo group (P < 0.001) in a sensitivity analysis.

SZC improved most secondary endpoints, including time to first hyperkalemia episode and spironolactone dose discontinuation due to hyperkalemia.

There were no significant differences in quality of life scores between the two groups at 6 months.

Heart failure events were higher in the SZC group (10% vs 2%), though cardiovascular deaths were equal in both groups.

Among patients with NT-proBNP ≤ 4,000 pg/mL, HF events were slightly more frequent in the SZC group than in the placebo group.

At 6 months, NT-proBNP levels were higher in the SZC group, but the difference was not statistically significant (P = 0.061).

Daily loop diuretic doses showed no difference between the SZC and placebo groups.

The cost of SZC remains a concern, with variable insurance coverage and annual costs around $10,000 in the US.

Clinicians must weigh the benefits of potassium binders against potential polypharmacy and financial burdens.

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Take-Home Points

1. SZC helps maintain normokalemia in hyperkalemic or at-risk HFrEF patients on MRAs.
2. The risk of hyperkalemia is a major barrier to optimal MRA therapy in real-world practice.
3. Adverse events with SZC are slightly higher, especially in patients with high NT-proBNP levels.
4. The sodium load in SZC raises concerns about heart failure and polypharmacy risks.
5. The high cost of SZC limits its accessibility, making patient selection critical.
6. Further research is needed to identify high-risk patients who will benefit most from potassium binders.