Core evidence clinical impact summary for patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate in the treatment of hyperkalemia

Outcome measure	Evidence	Implications
Disease-oriented evidence
Hyperkalemia	Clinical trials and one observational study	Patiromer and ZS9 consistently demonstrated efficacy in the treatment of hyperkalemia. A dose-dependent potassium-lowering effect occurred with both of these agents. Similar results were observed in subgroups of patients with chronic kidney disease and/or heart failure. Longer trial durations with patiromer indicate it may be preferred in chronic hyperkalemia. On the other hand, ZS9 appears to be the preferred agent for the treatment of acute hyperkalemia. The efficacy of SPS for chronic hyperkalemia was demonstrated in two small randomized clinical trials. However, overall efficacy is unclear, due to the observational nature of past studies and short follow-up periods.
Patient-oriented evidence
Renin–angiotensin–aldosterone system-inhibitor utilization	Clinical trials and one observational study	Iloperidone was more effective than placebo and similar to haloperidol, risperidone, and ziprasidone in several psychometric scales and in symptoms assessment.
Safety	Clinical trials and one observational study	Patiromer and ZS9 were generally well tolerated. The most common adverse events were nausea, constipation, and diarrhea, and were mild in severity. Side effects of hypokalemia, hypomagnesemia, and gastrointestinal effects were less frequent with ZS9 compared to patiromer and SPS. In addition to these adverse events, the use of SPS has been associated with hypocalcemia, hypernatremia, and rare gastrointestinal effects of mucosal damage and intestinal necrosis.