Sodium zirconium cyclosilicate (SZC) helped to optimize spironolactone use in patients with heart failure and reduced ejection fraction (HFrEF) and hyperkalemia, based on findings from the REALIZE-K trial presented at AHA 2024 and published in JACC. Mineralocorticoid receptor antagonists like spironolactone have been shown to improve outcomes in patients with HFrEF but are underused, in part due to hyperkalemia, researchers said.

The study randomized 203 participants to either SZC or placebo. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/daily); those with hyperkalemia started SZC. Participants with normokalemia (potassium 3.5–5.0 mEq/L) on SZC and spironolactone ≥25 mg/daily were randomized to continued SZC or placebo for six months.

Findings showed the use of SZC led to more participants achieving the primary endpoint of normokalemia while on ≥25 mg/daily dose of spironolactone and not requiring rescue therapy for hyperkalemia, compared with placebo (71% vs. 36%, respectively). SZC also improved four out of five hierarchically tested secondary endpoints, including time to first hyperkalemic event and time to first discontinuation or down-titration of spironolactone.

Although underpowered for clinical outcomes, Mikhail N. Kosiborod, MD, FACC, et al., did note that more participants experienced worsening heart failure events with SZC (13 events) than with placebo (4 events) – a finding that should be factored into clinical decision making, they said.