Sodium Zirconium Cyclosilicate for Renin-Angiotensin-Aldosterone System Inhibitor Optimization in Patients with Heart Failure with Reduced Ejection Fraction: A Retrospective Analysis.

Abstract

In this retrospective analysis, we evaluate the effectiveness of the potassium (K+) binder sodium zirconium cyclosilicate (SZC) in maintaining normokalemia and facilitating the initiation, optimization, and maintenance of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). A total of 44 patients with HFrEF and a history of hyperkalemia who were receiving SZC to enable the prescription of RAASi were identified from two district general hospital sites. Retrospective analysis was performed to determine biochemical response, alterations in pharmacotherapy, and subsequent HF outcomes following initiation of SZC. Mean K+ was reduced by 0.9mmol/L within 1month of initiation of SZC; mean K+ after 12months of treatment was 4.8mmol/L with a median (interquartile range) duration of treatment of 13 (8.4-15.1) months. Following SZC treatment, 100% of patients received an angiotensin receptor-neprilysin inhibitor (18% increase) and 93% received a mineralocorticoid receptor antagonist (41% increase), with 59% and 37% achieving guideline-recommended dosing, respectively. Ninety-one percent of patients were able to receive triple or quadruple therapy with the addition of a beta-blocker and a sodium glucose co-transporter2 inhibitor. Reduced rates of hospitalization for HF (HHF) were observed with 12 episodes per 100 patient-years recorded (reduced from 21) in addition to improvements in mean left ventricular ejection fraction (29-36%) and median N-terminal pro-B-type natriuretic peptide (3458-2055ng/L, 45% median reduction). Renal function (creatinine clearance increased from 48.4 to 49.3ml/min) and systolic blood pressure (decreased from 124 to 122mmHg) were similar following optimization, and no tolerability issues were identified. Extended real-world treatment with the K+ binder SZC was effective at maintaining normokalemia, and was associated with a greater uptake of RAASi, a reduced rate of HHF, and improvements in cardiac biomarkers in patients with HFrEF.