Abstract 17489: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Once-Daily ZS-9 for Treatment of Hyperkalemia: Achievement and Maintenance of K+ in Subgroup Analysis of Patients with Heart Failure not on RAAS Inhibitors
Introduction: RAAS inhibitors (RAASi) have demonstrated improved outcomes for HF patients (pts) when given at high doses, but optimal treatment is limited by hyperkalemia (HK), eg, spironolactone withdrawal for K+ >5.0 mEq/L (per package insert). Thus, HF pts do not benefit from these life-saving therapies due to HK. Current HK therapies (ie, SPS) have inconsistent and questionable efficacy and carry significant GI intolerability. ZS-9, a nonabsorbed cation exchanger that selectively traps K+ in the gut, acutely restored and maintained K+ in HK pts in a large Phase 3 study. To evaluate pts for whom HK was potentially RAASi-limiting, HF pts not on RAASi were evaluated.
Methods: Pts (N=753) with K+ 5.0-6.5 mEq/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10g) or placebo (PBO) orally 3x/day for 48hr (acute phase). Following this phase, pts with K+ 3.5-5.0 mEq/L (n=542) were randomized 1:1 to the same ZS-9 acute phase dose or PBO 1x/day on Days 3-15 (extended phase). Unpaired t-tests were used to compare serum K+ in pts treated with ZS-9 vs PBO.
Results: Of 753 pts, 83 (11%) had HF and were not on RAASi; 13 were in the 10g dose group. Mean baseline (BL) K+ for these pts was 5.3 mEq/L. At 48hr (acute phase), K+ declined significantly, compared with BL (-0.73 mEq/L; p<0.05). In the extended phase, pts who remained on ZS-9 (n=6) maintained K+ (BL: 4.5 mEq/L, Day 15: 4.6 mEq/L; Figure). Of note, 86.4% of pts in the 10g dose group were normokalemic at 48hr, compared with only 47.8% of pts in the PBO group.
Conclusions: In HF pts not on RAASi, ZS-9 was effective at restoring and maintaining normokalemia, suggesting that these patients were potential candidates for RAASi. The high percentage of pts on PBO who did not restore normokalemia is representative of real-life pts for whom HK may limit optimal RAASi. To support the potential for ZS-9 to enable optimal cardio-and renoprotection by RAASi, further studies that evaluate the ability to challenge HF pts with RAASi after HK resolution are warranted.
Author Disclosures: B. Singh: Research Grant; Modest; ZS Pharma, Keryx, Concert, Amgen, La Jolla Pharma, Questcor, La Jolla Pharma. Honoraria; Modest; Amgen. Consultant/Advisory Board; Modest; ZS Pharma, Concert, Amgen, Questcor, Concert, Keryx. Employment; Significant; ZS Pharma, as of 8/1/2014. After clinical trial was finished.. Speakers Bureau; Significant; Questcor. H.S. Rasmussen: Employment; Significant; ZS Pharma, Inc.. Ownership Interest; Significant; ZS Pharma, Inc. P.T. Lavin: Employment; Significant; Boston Biostatistics Research Foundation, Lavin Consulting, LLC. Consultant/Advisory Board; Significant; ZS Pharma, Inc. A. Yang: Employment; Significant; Xelay Acumen, Inc.. Ownership Interest; Significant; ZS Pharma, Inc.. Consultant/Advisory Board; Significant; ZS Pharma, Inc. D.K. Packham: Research Grant; Modest; ZS Pharma, Inc.. Honoraria; Modest; Abbott, REATA, Mesoblast. Consultant/Advisory Board; Modest; ZS Pharma, Inc..
- © 2014 by American Heart Association, Inc.