Renin-Angiotensin-Aldosterone System Inhibitor Dosing After Initiation of Outpatient Sodium Zirconium Cyclosilicate Therapy: The GALVANIZE RAASi Real-World Evidence Study
Advances in Therapy, 2025
Introduction
The use of renin-angiotensin-aldosterone system inhibitors (RAASi), including mineralocorticoid receptor antagonists (MRAs), can cause or exacerbate hyperkalemia, especially in patients with chronic kidney disease (CKD) and heart failure (HF). Prior research has demonstrated that sodium zirconium cyclosilicate (SZC) can enable continued RAASi use in patients with hyperkalemia. This study, GALVANIZE RAASi, sought to describe the proportion of patients with hyperkalemia who had an optimized or maximized RAASi dose after the initiation of outpatient SZC therapy.
Methods
Using data from a large US insurance claims database from July 2018-December 2022, adults initiating SZC in the outpatient setting (index) while using a RAASi (≥ 7 day overlap with index and ≥ 1 RAASi fill in the 6-month follow-up period) were selected. Sub-studies included patients with baseline diagnosis codes for CKD or HF and patients with ≥ 1 MRA prescription during follow-up. The proportion of patients with an optimized (≥ 50% of target dose) or maximized (≥ 100% of target dose) RAASi dose during follow-up was described.
Results
Of the 2973 patients meeting study inclusion criteria who were included in the overall sample, 2549 were included in the CKD sub-study, 879 in the HF sub-study and 395 in the MRA sub-study. In the overall sample, 63.7% of patients had an optimized RAASi dose and 27.2% of patients had a maximized RAASi dose during follow-up, and the results were similar across sub-studies (optimized RAASi dose: 62.9-72.6%; maximized RAASi dose: 26.9-36.1%).
Conclusion
In this real-world study of patients with RAASi use after SZC initiation, about two-thirds of patients had an optimized RAASi dose and more than a quarter of patients had a maximized RAASi dose within 6 months of starting SZC. Findings were consistent across sub-studies of patients with CKD, HF and treatment with MRA. SZC may support the maintenance of optimal RAASi therapy; however, further comparative analyses are warranted. Graphical abstract available for this article.
Authors
Agiro A, Greatsinger A, Mu F, Cook EE, Chen J, Sundar M, Zhao A, Colman E, Malhotra A