The role of sodium zirconium cyclosilicate drug utilization in managing hyperkalemia: impact on healthcare resource utilization and on maintenance of renin-angiotensin-aldosterone system inhibitor therapy in Italian clinical practice

Hyperkalemia (HK) is prevalent in patients with chronic kidney disease (CKD) and heart failure, particularly those on renin-angiotensin-aldosterone system inhibitors (RAASi). However, HK treatment often necessitates RAASi discontinuation. Sodium zirconium cyclosilicate (SZC), reimbursed in Italy since 2021, offers a new treatment option for HK. This study aimed to assess real-world SZC use and resulting economic rebounds in Italy. Using administrative databases of healthcare entities covering about 6 million residents, patients with at least one prescription of SZC from Jan-2022 to Jun-2023 were identified. Patients receiving other potassium binders after SZC initiation were excluded. A logistic regression model estimated odds ratios (OR) with 95% confidence interval (95%CI) for predictors of long-term SZC use (&gt;90 days), including age, sex, CKD status, and comorbidities. Univariate regression identified the potential association between each individual predictor and the likelihood of long-term treatment, followed by multivariate analysis adjusted for confounders. A backward stepwise logistic regression method retained only significant predictors, enhancing model accuracy. The study identified 355 SZC-treated patients (mean age 70.4 years, 64.2% male). CKD was found in 69.3% (47.6% on dialysis), with common comorbidities including hypertension (57.5%), diabetes (43.4%), and heart failure (23.4%). RAASi use was observed in 68.7% before SZC initiation, and RAASi discontinuation was lower in long-term SZC users compared to short-term SZC users (41.2 vs. 56.6%, <i>p</i> = 0.048). Short-term SZC treatment (≤90 days) was more frequent (83.1%) and predicted by dialysis (OR = 0.22). Healthcare costs over 6 months averaged €7,943 for short-term users (dialysis: €3,452) and €6,647 for long-term users (dialysis: €1,130). This real-world study showed that nearly 17% of patients continued SZC therapy for ≥90 days. Long-term therapy was associated with lower RAASi discontinuation and reduced healthcare costs due to hospitalizations and outpatient specialist services, suggesting that SZC can potentially provide clinical and economic benefits for HK management.