Table 3: Evidence for Sodium Zirconium Cyclosilicate in Heart Failure: Randomised and Observational Data.

Study	Design	Population	Primary/key Outcome	Key Findings	Limitations
REALIZE-K 202527	Randomised, double-blind, randomised-withdrawal trial	HFrEF (NYHA II–IV, LVEF ≤40%) with prevalent or incident MRA-associated hyperkalaemia; n=203	Optimal treatment response: normokalaemia while receiving spironolactone ≥25 mg/day without rescue therapy	Achieved in 71% with SZC versus 36% with placebo (OR 4.45; 95% CI [2.89–6.86]; p<0.001)	Not powered for clinical outcomes; exploratory analysis showed numerically higher HF events in SZC arm
Hida et al. 202528	Retrospective cohort study	Systolic HF (LVEF <50%) with baseline hyperkalaemia; n=61	Composite of all-cause mortality or HF readmission at 2 years	Lower event rate with long-term SZC continuation (29% versus 47%; p=0.079)	Small sample; observational design; non-significant trend
Shimada et al. 202529	Retrospective comparative effectiveness study (IPTW-adjusted)	HF patients initiating potassium-binding therapy; n=12,918	HF hospitalisation; MRA continuation	SZC associated with higher HF hospitalisation risk versus CPS (HR 1.36; 95% CI [1.06–1.75]) and higher MRA continuation (70.1% versus 59.0%)	Residual confounding likely; CPS comparator limits generalisability

CPS = calcium polystyrene sulfonate; HF = heart failure; HFrEF = heart failure with reduced ejection fraction; IPTW = inverse probability of treatment weighting; LVEF = left ventricular ejection fraction; MRA = mineralocorticoid receptor antagonist; NYHA = New York Heart Association; SZC = sodium zirconium cyclosilicate.