SZC for RAASi Maximization Among Patients With CKD, HFrEF

Maximal dosing of renin-angiotensin-aldosterone inhibitors (RAASi) for patients with heart failure and reduced ejection fraction (HFrEF) can reduce hospitalization and mortality. However, when chronic kidney disease (CKD) is also present, the risk of hyperkalemia introduces challenges to optimal RAASi dosing.

Debasish Banerjee and colleagues studied the role the potassium binder sodium zirconium cyclosilicate (SZC) might play in maximizing RAASi without resultant hyperkalemia in patients with HFrEF and moderate to severe CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²).

Their double-blind, placebo-controlled trial included 112 participants, randomized to SZC (n=53) or placebo (n=59) with two weekly interventions. Study outcomes included the percentage of patients in each arm reaching the target dose of RAASi without experiencing hyperkalemia (serum potassium >5.5 mmol/L) or severe hyperkalemia (serum potassium >6.0 mmol/L) and the number of patients developing hyperkalemia or severe hyperkalemia.

The mean (± SD) participant age was 74±11 years, 73% were male, and 67% were White. In addition, 54% had diabetes, 11% were current smokers, 62% had a history of ischemic heart disease, and 35% had CKD stages 4-5. Baseline eGFR was 35±12 mL/min/1.73 m². Baseline characteristics were well matched between the two groups. Sacubitril/valsartan and eplerenone were the most common types of RAASi used.

On average, serum potassium levels increased in both the SZC and placebo groups by 0.03 mmol/L (95% CI, 0.005-0.05; P=.015) biweekly during the follow-up period. However, average serum potassium throughout the study period was 0.32 mmol/L (95% CI, 0.23-0.40; P<.001) lower in the SZC group than in the placebo group, accounting for the follow-up period.

Forty-three (39%) participants achieved the maximal RAASi dose without hyperkalemia: 21 (40%) in the SZC group and 22 (38%) in the placebo group. There was no statistical difference between the two groups (P=.792). Nineteen of 32 (59%) participants in the SZC group reached half the maximum dose of RAASi from less than half the dose compared with 10 of 23 (43%) patients in the placebo group, without hyperkalemia. There was no statistical difference between the two groups (P=.283).

Forty-one patients developed hyperkalemia (serum potassium >5.5 mmol/L) over the study period: 27 (47%) in the placebo group and 14 (27%) in the SZC group (P=.040). Four patients in the SZC group and 12 patients in the placebo group developed severe hyperkalemia (serum potassium >6.0 mmol/L; P=.059).

The authors concluded that, “In this study of rapid RAASi maximization, hyperkalemia (>5.5 mmol/L) was more common in patients on placebo compared to SZC; however, there was no statistically significant difference in proportion of patients who reached target dose of RAASi in CKD patients with HFrEF.”

Source: Banerjee D, Ster IC,  Ali M, et al. Maximisation of renin-angiotensin-aldosterone inhibitors in heart failure patients with CKD using potassium binder; preliminary analysis of a randomised double-blind placebo-controlled trial. Abstract #WCN25-4625. Presented at the World Congress of Nephrology; February 6-9, 2025; New Delhi, India. Funding was provided by an externally sponsored research program of AstraZeneca.