Abstract 13555: Acute Efficacy of Sodium Zirconium Cyclosilicate (ZS-9) in Patients on Mineralocorticoid-Receptor Antagonists: Analysis From Two Phase 3 Studies
Introduction: Although mineralocorticoid-receptor antagonists (MRAs) are strongly recommended by guidelines for chronic management of patients with heart failure (HF), less than 1/3 of eligible patients receive these cardio-protective medications due to the risk of hyperkalemia (hyperK; potassium [K+] ≥5.1 mEq/L). Sodium zirconium cyclosilicate (ZS-9) is a highly selective K+ ion trap that binds K+ throughout the GI tract. We examined the effectiveness of ZS-9 in treating hyperK in patients receiving MRAs using pooled data from 2 recently completed Phase 3 clinical trials.
Methods: Data were pooled from 2 Phase 3 trials of patients with hyperK: ZS003 (N=753) and HARMONIZE (N=258). In both trials, patients receiving MRAs at baseline, and treated with 10 g, three times daily (TID), ZS-9 for 48 hrs were selected. Per protocol, MRA doses remained stable for the duration of the study. We examined absolute change in K+ from baseline, proportion of patients who achieved normokalemia by 24 and 48 hrs, and time to K+ normalization.
Results: Across studies, 19 patients were on MRAs (age 73y; 74% HF; 90% eGFR <60; 74% diabetes mellitus). Mean baseline K+ was 5.7 mEq/L. ZS-9 significantly reduced K+ during 48 hrs after treatment initiation (Figure): by 0.3, 0.5, 0.5, 0.7 and 1.1 mEq/L at 1, 2, 4, 24 and 48 hrs, respectively (P<0.005 for each time point vs. baseline). Normokalemia was achieved in 84% and 95% of patients by 24 and 48 hours, respectively. Median time to K+ normalization was 3.8 hrs. During the initial 48 hrs of treatment of the overall population treated with 10 g ZS-9, the adverse event rate was 9% compared to 11% among patients who received placebo.
Conclusions: In patients with hyperK while on MRA therapy, ZS-9 rapidly lowered K+ to normal range, with 95% of patients achieving normokalemia by 48 hrs. If confirmed in future studies, these results suggest that ZS-9 may enable optimization of cardio-protective MRA therapy in HF patients with or at high risk for hyperK.
Author Disclosures: M. Kosiborod: Consultant/Advisory Board; Significant; ZS Pharma, Inc.. P.A. McCullough: None. H. Rasmussen: Employment; Significant; ZS Pharma, Inc.. Ownership Interest; Significant; ZS Pharma, Inc. B. Singh: Employment; Significant; ZS Pharma, Inc.. Ownership Interest; Significant; ZS Pharma, Inc. P.T. Lavin: Consultant/Advisory Board; Significant; ZS Pharma, Inc.. P. Deedwania: None.
- © 2015 by American Heart Association, Inc.