Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia: REALIZE-K Design and Baseline Characteristics

Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilic...

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Detalles Bibliográficos
Autores: Kosiborod MN, Cherney D, Connelly K, Desai AS, Guimarães PO, Kuthi L, Lala A, Madrini V Jr, Merkely B, Villota JN, Squire I, Testani JM, Vaclavik J, Verma S, Wranicz J, Dahl M, Eudicone JM, Friberg L, Petrie MC
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p19058
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/19058
Access Level:acceso abierto
Palabra clave:KEY WORDS guideline-directed medical therapy
heart failure
hyperkalemia
mineralocorticoid receptor antagonists
sodium zirconium silicate
Descripción
Sumario:Background: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. Objectives: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). Methods: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction <= 40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone >= 25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone >= 25 mg daily, no rescue for hyperkalemia [months 1-6]). Results: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m(2), 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. Conclusions: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia.