#1287 Duration of sodium zirconium cyclosilicate treatment and continuation of RAASi therapy after a hyperkalaemia episode
Authors: Arroyo David , Pollack Charles V , Kanda Eiichiro , Lázaro Ignacio José Sánchez , Lesén Eva , Franzén Stefan , Gray Christen M , Murohara Toyoaki , Rastogi Anjay 
Published: May 2024

Abstract

Background and Aims
Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is foundational in the management of chronic kidney disease (CKD) and heart failure (HF) but increases the risk of hyperkalaemia (HK). Current guidelines recommend continuation of RAASi therapy while managing risk of HK using novel potassium binders, such as sodium zirconium cyclosilicate (SZC). This study describes the likelihood of continued RAASi therapy after a HK episode by SZC treatment duration in routine clinical practice across three countries.

Method
This observational study used contemporary data from healthcare registries and claims in the US, Japan and Spain, and included non-dialysis patients diagnosed with CKD and/or HF who initiated outpatient treatment with SZC while on RAASi therapy. The duration of SZC treatment and continuation of RAASi therapy were described using the Kaplan–Meier method. The association between time on SZC treatment and continuation of RAASi therapy is being analysed by applying Hernàn's randomised trial emulation approach (using cloning, censoring and weighting) to avoid the risk of immortal time bias. A weighted Kaplan–Meier method with bootstrapping will be used to estimate the likelihood of continued RAASi treatment at, e.g. 180 days by SZC treatment duration strategy, e.g. 1–30, 31–60 days, etc. The corresponding association will be evaluated using the z-test where the estimated probabilities are compared between strategies.

Results
This study included 4008 patients who initiated outpatient treatment with SZC, across the US (3137), Japan (655) and Spain (216). For the US, Japan and Spain, respectively, mean age was 72.9, 76.0 and 72.6 years; 54.4%, 62.9% and 58.3% were male; 95.8%, 71.9% and 94.4% had CKD; and 39.8%, 79.1% and 36.1% had HF. In the US, 31.5% (95% CI 29.8–33.2%) were treated with SZC for at least 60 days, and 14.4% (95% CI 13.1–15.8%) were treated for at least 120 days. Among US patients still on SZC treatment at 120 days, 84.0% (95% CI 81.2–86.8%) remained on RAASi therapy at that time, while the corresponding value for all SZC initiators, including those who discontinued SZC earlier, was 65.5% (63.7–67.3%). In Japan, 32.2% (95% CI 28.6–36.2%) were treated with SZC for at least 120 days and, of these, 92.3% (95% CI 89.3–95.4%) remained on RAASi therapy at that time. Among all SZC initiators (including the early discontinuers), 78.4% (95% CI 75.1–81.8%) remained on RAASi therapy at 120 days. In Spain, most patients (78.0% [95% CI 72.2–84.2%]) were treated with SZC for at least 120 days, and 84.6% (95% CI 79.4–90.2%) of these patients remained on RAASi therapy at that time. Analyses of the likelihood of continued RAASi treatment by SZC treatment duration strategy using Hernàn's approach are currently ongoing and will be presented at the congress.

Conclusion
This study provides contemporary insights into the management of HK with the novel potassium binder SZC across three different countries and demonstrates that duration of SZC treatment is positively associated with continued guideline-directed RAASi therapy after a HK episode.