Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis

Background Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK(+)) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. Method We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. Results Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK(+) (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK(+) tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. Conclusions SZC effectively decreased the sK(+) level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

Automated summary

Oral sodium zirconium cyclosilicate (SZC) effectively reduces serum potassium levels in patients with hyperkalemia within 48 hours, and continued use helps in long-term potassium control, showing a favorable safety profile.