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.
Keywords: Chronic kidney disease; Heart failure; Hyperkalemia; Mineralocorticoid receptor antagonists; Optimized dose; Real-world evidence; Renin-angiotensin-aldosterone system inhibitors; Sodium zirconium cyclosilicate.
Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is often used to manage blood pressure and protect the heart and kidneys in people with conditions like heart failure and chronic kidney disease. Hyperkalemia, a condition of high potassium levels, often limits RAASi use, particularly for patients with chronic kidney disease or heart failure, including patients who receive a class of RAASi therapy called mineralocorticoid receptor antagonists. This study described the proportion of patients with an optimized or maximized RAASi dose among patients with hyperkalemia who started sodium zirconium cyclosilicate (SZC) in the outpatient setting. The study analyzed data from US insurance claims (2018–2022) for patients who started SZC alongside RAASi and continued RAASi for at least 6 months. Of 2973 patients meeting the inclusion criteria, 2549 had chronic kidney disease, 879 had heart failure, and 395 used mineralocorticoid receptor antagonist treatments. During the 6-month follow-up, 63.7% of patients achieved optimized RAASi doses (at least 50% of the target dose), while 27.2% reached maximized doses (100% of the target dose), with similar trends across chronic kidney disease, heart failure and mineralocorticoid receptor antagonists sub-studies. These results suggest SZC may play a role in supporting the maintenance of optimal RAASi therapy for patients at risk of hyperkalemia, providing consistent benefits across sub-studies. Further studies are recommended to confirm these findings and explore comparative outcomes.
© 2025. The Author(s).