#1302 Maintained renin-angiotensin-aldosterone system inhibitor therapy with sodium zirconium cyclosilicate in patients with chronic kidney disease
Authors: Rastogi Anjay , Pollack Charles V , Lázaro Ignacio José Sánchez , Lesén Eva , Arnold Matthew , Franzén Stefan , Allum Alaster , Hernández Ignacio , Murohara Toyoaki , Kanda Eiichiro 
Published: May 2024

Abstract

Background and Aims
Hyperkalaemia is a barrier to achieving guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy. This observational cohort study compared the likelihood of maintained (stabilised or up-titrated) RAASi therapy at 6 months following an episode of hyperkalaemia in patients with chronic kidney disease (CKD) from the US and Japan, in patients who were treated with sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no potassium (K+) binder prescription.

Method
Using data from healthcare registers and hospital medical records, patients with CKD receiving RAASi therapy who had an episode of hyperkalaemia in an inpatient or outpatient care setting were identified. Propensity score (PS) matching (up to 1:4) was applied to balance the SZC cohort to a No K+ binder cohort on baseline characteristics. The proportions of patients in each cohort who had discontinued, down-titrated, stabilised or up-titrated their RAASi treatment at 6 months were described, with P values for differences between cohorts calculated using Chi-squared tests. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus No K+ binder cohorts, and a meta-analysis across countries was performed using a random effects model.

Results
After PS-matching, the SZC cohorts included 530 (US) and 211 (Japan) patients, and the No K+ binder cohorts included 1937 and 711 patients, respectively. Mean ages of patients were 72 (US) and 74 (Japan) years, and 44% and 30% were females, respectively. Most US patients had CKD Stage 3−4 (∼89%), while CKD Stage 5 was more common in Japan (∼47% of patients). Comorbid heart failure was less common in the US than in Japan (∼33% versus ∼74%, respectively). The proportions who discontinued RAASi therapy at 6 months were consistently lower in the SZC cohorts than in the No K+ binder cohorts in both countries (Table). At 6 months, 69.8% (US) and 79.6% (Japan) of the SZC cohorts had maintained their RAASi therapy, while corresponding proportions for the No K+ binder cohorts were 53.6% (US) and 52.6% (Japan). The odds ratios (95% confidence interval) for maintained RAASi therapy in the SZC cohort versus the No K+ binder cohort were 2.09 (1.70–2.58) in the US and 3.54 (2.43–5.17) in Japan; the meta-analysed odds ratio was 2.65 (1.62–4.34).

Conclusion
In contemporary routine clinical practice of patients with CKD, the likelihood ofstabilised or up-titrated RAASi therapy at 6 months following an episode of hyperkalaemia was substantially higher in patients treated with SZC for at least 120 days versus those with no prescribed K+ binder treatment. These data demonstrate the potential for SZC to facilitate maintained, guideline-concordant RAASi therapy following an episode of hyperkalaemia to achieve optimal treatment outcomes in patients with CKD.