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The following is a summary of “Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure,” published in the January 2025 issue of Cardiology by Kosiborod et al.
Mineralocorticoid receptor antagonists (MRA) enhance outcomes in heart failure with reduced ejection fraction (HFrEF), but with limited use, primarily due to hyperkalemia.
Researchers conducted a retrospective study to assess the effects of sodium zirconium cyclosilicate (SZC) in optimizing spironolactone use among participants with HFrEF and hyperkalemia.
They performed the REALIZE-K trial (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone). Participants with HFrEF; NYHA functional class II-IV; left ventricular ejection fraction ≤40%) on guideline-directed therapy (excluding MRA) and MRA-induced hyperkalemia were enrolled. During the open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia received SZC, participants with normokalemia (potassium: 3.5-5.0 mEq/L) and on spironolactone ≥25 mg/day were randomized to continue SZC or receive a placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]), 5 secondary endpoints were tested hierarchically, and exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits).
The results showed 203 participants were randomized (SZC: 102; placebo: 101). A higher proportion of SZC-treated participants achieved an optimal response compared to placebo (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001), SZC improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001), receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001), time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001), and time to decrease or discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). No significant difference was observed in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score at 6 months (−1.01 points; 95% CI: −6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were similar between SZC and placebo. A composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 CV death, 10 HF events) and 3 (3%) in the placebo group (1 CV death, 2 HF events; log-rank nominal P = 0.034).
Investigators concluded the SZC improved normokalemia and reduced the risk of hyperkalemia and spironolactone discontinuation in participants with HFrEF and hyperkalemia.