Abstract 16681: Effect of ZS-9 Treatment for Hyperkalemia in Patients With Heart Failure Receiving Maximal, Submaximal or no Renin-angiotensin-aldosterone-system Inhibitors: Pooled Analysis From Two Phase III Trials

Introduction: Renin-angiotensin-aldosterone-system inhibitors (RAASi) can decrease morbidity and mortality in patients (pts) with heart failure (HF), however, RAASi are often avoided or used in submaximal doses due to manifest or potential risk of hyperkalemia. Sodium zirconium cyclosilicate (ZS-9) is an investigational agent designed to be a selective cation exchanger that preferentially binds potassium (K + ) in exchange for H + and Na + throughout the gastrointestinal tract. This post-hoc analysis assessed the effects of ZS-9 in pts with HK on maximal doses of RAASi, submaximal RAASi, or no RAASi at baseline. Methods: Data for HF pts with hyperkalemia on RAASi (maximal or submaximal doses) and those not on RAASi were pooled from two phase III ZS-9 trials: ZS-003 and HARMONIZE. Both trials had an induction phase, where 153 HF pts received 10g ZS-9 TID for 48h, and a maintenance phase. Results: Among the 153 HF pts, 68 (44%) were on maximal RAASi doses, 43 (28%) were on submaximal doses, and 42 (28%) were not on RAASi. In the subgroup of pts on maximal and submaximal RAASi doses, mean (SD) K + declined from 5.47+/-0.38 and 5.47+/-0.44 mEq/L at baseline to 4.42+/-0.46 and 4.53+/-0.42 mEq/L at 48h in the induction phase (Figure); 91% and 86% of pts achieved normal K + by 24h and 99% and 98% achieved normal K + by 48h, respectively. Median time to K + normalization was 2.0 h (IQR 25-75: 1.0-21.9 and 1.0-22.9) for both groups. In the subgroup of HF pts not on RAASi, mean (SD) K + declined from 5.47+/-0.38 mEq/L at baseline to 4.43+/-0.46 mEq/L at 48h in the induction phase; 90% and 100% of pts achieved normal K + by 24h and 48h, respectively. Median time to K + normalization was 2.0 h (IQR 25-75: 1.0-4.3) in this group. In the overall pt population who received 10g ZS-9 during the induction phase (n=401), 9.2% of pts had AEs; the most common AEs were GI disorders (3.7%). Conclusions: ZS-9 restored normokalemia in hyperkalemic HF pts regardless of the presence or intensity of RAASi therapy at baseline.