Sodium zirconium cyclosilicate, hyperkalaemia, and spironolactone optimization in heart failure with reduced ejection fraction: The REALIZE-K open-label run-in phase

Mark C Petrie¹, David Z I Cherney², Akshay S Desai³, Jeffrey M Testani⁴, Subodh Verma⁵, Khaja Chinnakondepalli⁶, David Dolling⁷, Shachi Patel⁶, Magnus Dahl⁸, James M Eudicone⁹, Lovisa Friberg⁸, Mario Ouwens¹⁰, Murillo O Antunes¹¹, Kim A Connelly¹², Vagner Madrini Jr¹³, Luca Kuthi¹⁴, Anuradha Lala¹⁵, Miguel Lorenzo¹⁶, Patrícia O Guimarães¹³, Marta Cobo Marcos¹⁷, Béla Merkely¹⁴, David Gonzales-Calle¹⁸, Julio Nuñez Villota¹⁹, Iain Squire²⁰, Jan Václavík²¹, Jerzy Wranicz²², Mikhail N Kosiborod²³

Affiliations

¹ School of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
² University Health Network and Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada.
³ Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Section of Cardiovascular Medicine, Yale University, Guilford, CT, USA.
⁵ Institute of Unity Health Toronto and University of Toronto, Toronto, ON, Canada.
⁶ Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA.
⁷ Fortrea, Maidenhead, UK.
⁸ BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden.
⁹ BioPharmaceuticals Medical (Evidence), AstraZeneca, Wilmington, DE, USA.
¹⁰ BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
¹¹ Hospital Universitário São Francisco de Assis na Providência de Deus and Universidade São Francisco, Bragança Paulista, Brazil.
¹² Keenan Research Centre for Biomedical Science, Unity Health Division Head, Cardiology, St. Michael's Hospital, Toronto, ON, Canada.
¹³ Hospital Israelita Albert Einstein, São Paulo, Brazil.
¹⁴ Semmelweis University, Budapest, Hungary.
¹⁵ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine, New York, NY, USA.
¹⁶ Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
¹⁷ Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
¹⁸ Hospital Universitario de Salamanca, Salamanca, Spain.
¹⁹ Hospital Clinico Universitario de Valencia and University of Valencia, Valencia, Spain.
²⁰ NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
²¹ University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
²² Department of Electrocardiology, Medical University of Lodz, Łódź, Poland.
²³ Late-Stage Development, Cardiovascular, Renal and Metabolic, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.

PMID: 40879354
PMCID: PMC12482837
DOI: 10.1002/ejhf.3787

Sodium zirconium cyclosilicate, hyperkalaemia, and spironolactone optimization in heart failure with reduced ejection fraction: The REALIZE-K open-label run-in phase

Mark C Petrie et al. Eur J Heart Fail. 2025 Aug.

. 2025 Aug;27(8):1491-1495.

doi: 10.1002/ejhf.3787. Epub 2025 Aug 20.

Authors

Affiliations

¹ School of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
² University Health Network and Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada.
³ Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Section of Cardiovascular Medicine, Yale University, Guilford, CT, USA.
⁵ Institute of Unity Health Toronto and University of Toronto, Toronto, ON, Canada.
⁶ Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA.
⁷ Fortrea, Maidenhead, UK.
⁸ BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden.
⁹ BioPharmaceuticals Medical (Evidence), AstraZeneca, Wilmington, DE, USA.
¹⁰ BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
¹¹ Hospital Universitário São Francisco de Assis na Providência de Deus and Universidade São Francisco, Bragança Paulista, Brazil.
¹² Keenan Research Centre for Biomedical Science, Unity Health Division Head, Cardiology, St. Michael's Hospital, Toronto, ON, Canada.
¹³ Hospital Israelita Albert Einstein, São Paulo, Brazil.
¹⁴ Semmelweis University, Budapest, Hungary.
¹⁵ Mount Sinai Fuster Heart Hospital, Icahn School of Medicine, New York, NY, USA.
¹⁶ Hospital Clínico Universitario de Valencia, University of Valencia, Valencia, Spain.
¹⁷ Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
¹⁸ Hospital Universitario de Salamanca, Salamanca, Spain.
¹⁹ Hospital Clinico Universitario de Valencia and University of Valencia, Valencia, Spain.
²⁰ NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
²¹ University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
²² Department of Electrocardiology, Medical University of Lodz, Łódź, Poland.
²³ Late-Stage Development, Cardiovascular, Renal and Metabolic, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.

PMID: 40879354
PMCID: PMC12482837
DOI: 10.1002/ejhf.3787

No abstract available

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Figures

**Figure 1**
REALIZE‐K run‐in phase: chronic heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%), hyperkalaemia, sodium zirconium cyclosilicate (SZC), and titration of spironolactone. K⁺, potassium; MRA, mineralocorticoid receptor antagonist.

See this image and copyright information in PMC

References

1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022;145:e895–e1032. 10.1161/CIR.0000000000001063 - DOI - PubMed
1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2022;24:4–131. 10.1002/ejhf.2333 - DOI - PubMed
1. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709–717. 10.1056/NEJM199909023411001 - DOI - PubMed
1. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al.; EMPHASIS‐HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21. 10.1056/NEJMoa1009492 - DOI - PubMed
1. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical therapy for heart failure with reduced ejection fraction: The CHAMP‐HF registry. J Am Coll Cardiol 2018;72:351–366. 10.1016/j.jacc.2018.04.070 - DOI - PubMed

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Sodium zirconium cyclosilicate, hyperkalaemia, and spironolactone optimization in heart failure with reduced ejection fraction: The REALIZE-K open-label run-in phase

Affiliations

Sodium zirconium cyclosilicate, hyperkalaemia, and spironolactone optimization in heart failure with reduced ejection fraction: The REALIZE-K open-label run-in phase

Authors

Affiliations

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources