Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients

Results from a phase 3 randomized, double-blind, placebo-controlled trial

Stefan D. Anker, Mikhail Kosiborod, Faiez Zannad, Ileana L. Pina, Peter A. McCullough, Gerasimos Filippatos, Peter Van Der Meer, Piotr Ponikowski, Henrik S. Rasmussen, Philip T. Lavin, Bhupinder Singh, Alex Yang, Prakash Deedwania

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Aims Hyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS-9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZE - a Phase 3, double-blind, randomized, placebo-controlled trial. In the present study we evaluated management of serum potassium with daily ZS-9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies. Methods and results Heart failure patients with evidence of hyperkalaemia (serum potassium ≥5.1 mmol/L, n = 94) were treated with open-label ZS-9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5-5.0 mmol/L) were randomized to daily ZS-9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8-29 post-randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS-9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P

Original languageEnglish (US)
Pages (from-to)1050-1056
Number of pages7
JournalEuropean Journal of Heart Failure
Volume17
Issue number10
DOIs
StatePublished - Oct 1 2015

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Potassium
Heart Failure
Placebos
Maintenance
Serum
Renin-Angiotensin System
Hyperkalemia
ZS-9 compound
Upper Gastrointestinal Tract
Random Allocation
Duodenum
Oral Administration
Reference Values
Randomized Controlled Trials
Ions

Keywords

  • heart failure
  • hyperkalaemia
  • RAAS
  • ZS-9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients : Results from a phase 3 randomized, double-blind, placebo-controlled trial. / Anker, Stefan D.; Kosiborod, Mikhail; Zannad, Faiez; Pina, Ileana L.; McCullough, Peter A.; Filippatos, Gerasimos; Van Der Meer, Peter; Ponikowski, Piotr; Rasmussen, Henrik S.; Lavin, Philip T.; Singh, Bhupinder; Yang, Alex; Deedwania, Prakash.

In: European Journal of Heart Failure, Vol. 17, No. 10, 01.10.2015, p. 1050-1056.

Research output: Contribution to journalArticle

Anker, SD, Kosiborod, M, Zannad, F, Pina, IL, McCullough, PA, Filippatos, G, Van Der Meer, P, Ponikowski, P, Rasmussen, HS, Lavin, PT, Singh, B, Yang, A & Deedwania, P 2015, 'Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: Results from a phase 3 randomized, double-blind, placebo-controlled trial', European Journal of Heart Failure, vol. 17, no. 10, pp. 1050-1056. https://doi.org/10.1002/ejhf.300
Anker, Stefan D. ; Kosiborod, Mikhail ; Zannad, Faiez ; Pina, Ileana L. ; McCullough, Peter A. ; Filippatos, Gerasimos ; Van Der Meer, Peter ; Ponikowski, Piotr ; Rasmussen, Henrik S. ; Lavin, Philip T. ; Singh, Bhupinder ; Yang, Alex ; Deedwania, Prakash. / Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients : Results from a phase 3 randomized, double-blind, placebo-controlled trial. In: European Journal of Heart Failure. 2015 ; Vol. 17, No. 10. pp. 1050-1056.
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abstract = "Aims Hyperkalaemia in heart failure patients limits use of cardioprotective renin-angiotensin-aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS-9) is a selective potassium ion trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS-9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZE - a Phase 3, double-blind, randomized, placebo-controlled trial. In the present study we evaluated management of serum potassium with daily ZS-9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies. Methods and results Heart failure patients with evidence of hyperkalaemia (serum potassium ≥5.1 mmol/L, n = 94) were treated with open-label ZS-9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5-5.0 mmol/L) were randomized to daily ZS-9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8-29 post-randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS-9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P",
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AU - Kosiborod, Mikhail

AU - Zannad, Faiez

AU - Pina, Ileana L.

AU - McCullough, Peter A.

AU - Filippatos, Gerasimos

AU - Van Der Meer, Peter

AU - Ponikowski, Piotr

AU - Rasmussen, Henrik S.

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AU - Singh, Bhupinder

AU - Yang, Alex

AU - Deedwania, Prakash

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