Comparative effectiveness of sodium zirconium cyclosilicate versus calcium polystyrene sulfonate for patients with heart failure.

Patients with heart failure (HF) are at increased risk of hyperkalemia, and implementing appropriate potassium-lowering therapy is essential for optimizing outcomes. Sodium zirconium cyclosilicate (SZC) is a selective potassium binder that effectively reduces serum potassium levels; however, its impact on mortality and cardiovascular outcomes in HF remains unclear. This study compared the effects of SZC and calcium polystyrene sulfonate (CPS) on a composite of all-cause death and major adverse cardiovascular event (MACE)-related hospitalization, along with individual MACE components and continuation rates of HF medications. We conducted a retrospective cohort study using data from the JMDC hospital database, including adult patients with HF who initiated SZC or CPS between April 2020 and September 2023 and continued treatment for at least 30 days. Propensity score-based inverse probability of treatment weighting (IPTW) and multivariable Cox models were used to control for confounding. A total of 12,918 patients were included (11,139 CPS; 1779 SZC), with a median follow-up of 147 and 138 days, respectively. After IPTW adjustment, baseline characteristics were balanced, except for the prescription year. The primary composite outcome (all-cause death or MACE hospitalization) occurred in 148 patients in the SZC group and 839 in the CPS group (Hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.94-1.43). In a post hoc analysis, the composite of all-cause death and HF hospitalization occurred in 143 vs. 793 patients (HR 1.21, 95% CI 0.98-1.50). SZC use was associated with a higher HR for HF hospitalization (103 vs. 524 events, HR 1.36, 95% CI 1.06-1.75) and a lower HR for stroke hospitalization (6 vs. 80 events, HR 0.33, 95% CI 0.12-0.91). Mineralocorticoid receptor antagonists (MRA) continuation was more frequent in the SZC group [70.1% vs. 59.0%, weighted odds ratio, 1.39 (95% CI 1.11-1.75)]. These findings suggest that although SZC may not improve survival or overall cardiovascular outcomes, it may help maintain essential HF therapies such as MRA.