Sodium zirconium cyclosilicate for MRAs optimization in HFrEF: lessons learned from the REALIZE-K trial.
In the REALIZE-K trial, sodium zirconium cyclosilicate enabled more patients with HFrEF and hyperkalemia to maintain normokalemia on optimal spironolactone dosing, though more heart-failure events occurred in the SZC arm, a signal that should factor into clinical decision-making.
Background
Mineralocorticoid receptor antagonists (MRAs) such as spironolactone improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are often underused because of hyperkalemia. REALIZE-K assessed whether sodium zirconium cyclosilicate (SZC), a selective potassium binder, could enable optimization and continuation of spironolactone in patients with HFrEF and MRA-induced hyperkalemia.
Study design
REALIZE-K was a prospective, double-blind, randomized-withdrawal trial in patients with HFrEF (NYHA class II-IV, left ventricular ejection fraction at most 40%) on optimal guideline-directed therapy except MRA. During open-label run-in, participants underwent spironolactone titration (target 50 mg/day) and those with hyperkalemia started SZC. Participants achieving normokalemia on SZC and spironolactone of at least 25 mg/day were randomized to continued SZC (102 patients) or placebo (101 patients) for 6 months, with optimal treatment response (normokalemia on spironolactone without rescue therapy) as the primary endpoint.
Key findings
A higher percentage of SZC- versus placebo-treated participants had an optimal response (71% vs 36%; odds ratio 4.45). SZC also improved the first four secondary endpoints, including normokalemia without rescue therapy (58% vs 23%) and continued spironolactone of at least 25 mg/day (81% vs 50%), and prolonged time to hyperkalemia. However, a composite of cardiovascular death or worsening heart failure occurred in 11 (11%) SZC participants versus 3 (3%) placebo participants (nominal P = 0.034), and there was no difference in Kansas City Cardiomyopathy Questionnaire score. Overall adverse and serious adverse events were balanced.
Clinical implications
SZC produced large improvements in maintaining normokalemia while on optimal spironolactone and reduced down-titration or discontinuation of spironolactone due to hyperkalemia. The trial was underpowered for clinical outcomes, but the higher number of heart-failure events observed with SZC should be weighed when applying these findings to MRA optimization in clinical practice.
Category
Research
Source
Heart Failure Reviews
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