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.

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<0.01 vs. each ZS-9 group); greater proportions of ZS-9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P < 0.01 vs. each ZS-9 group). The safety profile was consistent with previously reported overall study population.

CONCLUSION:

Compared with placebo, all three ZS-9 doses lowered potassium and effectively maintained normokalaemia for 28 days in heart failure patients without adjusting concomitant RAASi, while maintaining a safety profile consistent with the overall study population.

• Authors: Stefan D Anker, Mikhail Kosiborod, Faiez Zannad, Ileana L Piña, Peter A McCullough, Gerasimos Filippatos, Peter van der Meer, Piotr Ponikowski, Henrik S Rasmussen, Philip T Lavin, Bhupinder Singh, Alex Yang, Prakash Deedwania
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 17 Issue 10 Pg. 1050-6 (Oct 2015) ISSN: 1879-0844 [Electronic] England
• PMID: 26011677 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Chemical References

• Silicates
• sodium zirconium cyclosilicate
• Potassium

Topics

• Double-Blind Method
• Heart Failure (blood)
• Humans
• Hyperkalemia (blood, drug therapy)
• Potassium (blood)
• Silicates (therapeutic use)