Abstract 503: Maintenance of Normokalemia with ZS-9 Once Daily in CHF Patients on RAAS Inhibitors: Subgroup Analysis of a Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Hyperkalemia

Abstract

Risk of hyperkalemia (HK) limits the use of RAAS inhibitors (RAASi) in pts with congestive heart failure (CHF), chronic kidney disease (CKD), or diabetes. ZS-9, a nonabsorbed cation exchanger designed to preferentially entrap K + in the GI tract, significantly reduced serum K + vs placebo (PBO) over 48 hours with low rates of adverse events in CKD patients with hyperkalemia. A pre-specified subgroup analysis was conducted with CHF patients from a large Phase 3 trial of ZS-9 for HK. Pts (N=753) with K + 5.0-6.5 mmol/L were randomized (1:1:1:1:1) to ZS-9 (1.25, 2.5, 5 or 10 g) or PBO orally 3х daily for 48 hr (acute phase). At the end of this phase, pts with K + 3.5-5.0 mmol/L (n=542) were randomized 1:1 to the same ZS-9 acute phase dose or PBO once daily (QD) on Days 3-15 (extended phase); patients initially on PBO were randomized to 1.25 or 2.5g ZS-9 QD. RAASi were kept constant during the study. Serum K + in CHF pts treated with the highest ZS-9 dose (10g) was compared to PBO with an unpaired t-test. Among 753 pts, 300 (40%) had CHF at baseline (per investigator assessment), of whom 72% were on RAASi. Mean baseline K + was 5.3 mmol/L in the CHF pts. CHF pts who entered the Extended Phase (n=204) either remained on ZS-9 10g (n=26) or switched to PBO (n=23). The extended phase baseline K + was similar between groups (4.4 vs 4.5 mmol/L) and to the overall group (4.5 mmol/L ZS-9 [n=63] vs 4.4 mmol/L PBO [n=61]). On Day 15, mean K + for CHF patients on ZS-9 10g was 4.5 mmol/L vs 5.0 mmol/L for PBO (P=0.002; Fig). ZS-9 10g once daily maintained mean serum K + <5.0 mmol/L in pts with CHF despite RAASi continuation in most pts, indicating that ZS-9 permits optimal cardiorenal protection with RAASi for this population.