Systematic Review and Meta-Analysis of Patiromer and Sodium Zirconium Cyclosilicate: A New Armamentarium for the Treatment of Hyperkalemia.

OBJECTIVE: To compare and contrast the efficacy and safety of patiromer and sodium zirconium cyclosilicate (ZS-9) in the treatment of hyperkalemia. DESIGN: A systematic review and meta-analysis of phase II and III clinical trial data was completed. PATIENTS OR PARTICIPANTS: Eight studies (2 phase II and 4 phase III trials with 2 subgroup analyses) were included in the qualitative analysis whereas six studies (2 phase II and 4 phase III trials) were included in the meta-analysis. MEASUREMENTS AND RESULTS: There was significant heterogeneity in the meta-analysis with an I(2) value ranging from 80.6-99.6%. A random-effects meta-analysis was applied for all endpoints. Each clinical trial stratified results by hyperkalemia severity and dosing; therefore, these were considered separate treatment groups in the meta-analysis. For patiromer, there was a significant -0.70mEq/L (95% confidence interval [CI] -0.48 to -0.91mEq/L) change in potassium at 4 weeks. At day 3 of patiromer treatment, potassium change was -0.36mEq/L (range of standard deviation: 0.07 to 0.30). The primary endpoint for ZS-9- change in potassium at 48 hours- was -0.67mEq/L (95% CI -0.45 to -0.89mEq/L). By 1 hour after ZS-9 administration, change in potassium was -0.17mEq/L (95% CI -0.05 to -0.30). Analysis of pooled adverse effects from these trials indicates that patiromer was associated with more gastrointestinal upset (7.6% constipation, 4.5% diarrhea) and electrolyte depletion (7.1% hypomagnesemia), whereas ZS-9 was associated with adverse effects of urinary tract infections (1.1%) and edema (0.9%). CONCLUSION: Patiromer and ZS-9 represent significant pharmacologic advancements in the treatment of hyperkalemia. Both agents exhibited statistically and clinically significant reductions in potassium for the primary endpoint of this meta-analysis. Given the adverse effect profile and the observed time dependent effects, ZS-9 may play more of a role in treating acute hyperkalemia. This article is protected by copyright. All rights reserved.