{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:08:53Z","timestamp":1791446933504,"version":"4.3.3"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":3871,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"ZS Pharma Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Hyperkalaemia in heart failure patients limits use of cardioprotective renin\u2013angiotensin\u2013aldosterone 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\u2014a 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Heart failure patients with evidence of hyperkalaemia (serum potassium \u22655.1 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\u20135.0 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\u201329 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&amp;lt;0.01 vs. each ZS-9 group); greater proportions of ZS-9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P &amp;lt; 0.01 vs. each ZS-9 group). The safety profile was consistent with previously reported overall study population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.300","type":"journal-article","created":{"date-parts":[[2015,5,23]],"date-time":"2015-05-23T05:16:50Z","timestamp":1432358210000},"page":"1050-1056","source":"Crossref","is-referenced-by-count":166,"title":["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"],"prefix":"10.1093","volume":"17","author":[{"given":"Stefan D.","family":"Anker","sequence":"first","affiliation":[{"name":"Innovative Clinical Trials, Department of Cardiology & Pneumology, University Medical Centre G\u00f6ttingen (UMG) , Robert-Koch-Strasse 40, D\u201337075, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Kosiborod","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute and University of Missouri\u2013Kansas City , Kansas City, MO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Inserm, Universit\u00e9 de Lorraine , Vandoeuvre-Les-Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana L.","family":"Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Albert Einstein COM\/Montefiore Medical 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Wroc\u0142aw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik S.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"ZS Pharma, Inc. , Coppell, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip T.","family":"Lavin","sequence":"additional","affiliation":[{"name":"Boston Biostatistics Research Foundation , Framingham, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupinder","family":"Singh","sequence":"additional","affiliation":[{"name":"ZS Pharma, Inc. , Coppell, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Yang","sequence":"additional","affiliation":[{"name":"ZS Pharma, Inc. , Coppell, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Deedwania","sequence":"additional","affiliation":[{"name":"University of California San Francisco , 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