Efficacy and Tolerability of Sodium Zirconium Cyclosilicate or Patiromer in Managing Hyperkalemia: A Systematic Review and Meta-Analysis.

KEY POINTS: Both sodium zirconium cyclosilicate and patiromer effectively lower serum potassium and provide clinical benefits. Sodium zirconium cyclosilicate is associated with higher risk of edema. Patiromer is associated with the increased risk of constipation and hypokalemia.

BACKGROUND

Sodium zirconium cyclosilicate (SZC) and patiromer have recently been approved for the treatment of hyperkalemia. However, their efficacy in lowering serum potassium according to the phase of intervention, safety profile, and impact clinical outcomes remains to be fully defined. This study aims to assess their efficacy and tolerability in the management of hyperkalemia.

METHODS

A comprehensive search of PubMed, Scopus, and Cochrane Central Register of Controlled Trials was conducted up to June 6, 2025. Eligible studies included randomized controlled trials reporting the effects of SZC and patiromer on laboratory parameters, clinical outcomes, and safety profiles. Meta-analyses were synthesized using a random-effects model, with results presented as weighted mean differences (WMD) or relative risks (RR), along with 95% confidence intervals (CI).

RESULTS

Nineteen randomized controlled trials involving 3627 patients (1911 on SZC; 1716 on patiromer) were analyzed. During the initial 48-72 hours, only SZC significantly reduced serum potassium levels (WMD, -0.45 mEq/L; 95% CI, -0.61 to -0.29). At the end of treatment, both agents effectively lowered serum potassium (SZC: WMD, -0.50 mEq/L; 95% CI, -0.63 to -0.38; patiromer: WMD, -0.36 mEq/L; 95% CI, -0.51 to -0.21). SZC significantly normalized serum potassium and reduced hyperkalemia incidence, while patiromer enabled renin-angiotensin-aldosterone system inhibitor optimization by supporting target dosing and reducing discontinuation due to hyperkalemia. However, SZC was associated with a higher incidence of edema (RR, 2.92; 95% CI, 1.08 to 7.90) and patiromer with increased rates of constipation (RR, 2.96; 95% CI, 1.21 to 7.22) and hypokalemia (RR, 1.46; 95% CI, 1.05 to 2.03).

CONCLUSIONS

Both SZC and patiromer effectively lower serum potassium and provide clinical benefits, with distinct safety considerations. Therapy selection should be guided by treatment goals and the patient's individual risk profile.