Safety and efficacy of potassium binders on hyperkalemia: a novel systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Hyperkalemia is a common condition in patients with chronic kidney disease (CKD) and heart failure (HF), especially those receiving mineralocorticoid receptor antagonists and renin-angiotensin-aldosterone system inhibitors. It can increase the risk of arrhythmias and sudden death. Sodium Zirconium Cyclosilicate (SZC) and Patiromer are Potassium Binders (PB), a new therapies which is emerging to alternative for hyperkalemia in these patients, since they are capable of achieving a rapid reduction of serum potassium (sK+). However, the efficacy and safety of the new potassium binders in these populations remains uncertain. Purpose We aimed to conduct an up-dated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the use of SZC and Patiromer versus placebo in patients with hyperkalemia. Methods PubMed, Embase and Cochrane database were searched for randomized controlled trials which evaluates the treatment of hyperkalemia using PB, and reporting the following outcomes of effectiveness: (1) Mean Change sK+ and (2) Maintenance of normokalemia, and the safety outcomes: (3) Any adverse effects and (4) Serious adverse effects. The results were computed and pooled as risk ratio (RR) and mean difference (MD), using a random effects model and the confidence interval (CI) was assumed as 95%. Statistical analysis was performed in RStudio (Version 4.2.2) and heterogeneity was calculated using I2. Results We included 4,268 patients from 19 RCTs, of whom 61.1% were undergoing treatment with PB. Mean age of patients was 66±12.1 years and 36.5% were female. Patients who received Potassium binders had significant reduction of sK+ (MD -0,40 nmol/L, 95% CI: -0,62 -0,19; p0.01, Fig. 1A) compared with those receiving placebo. Additionally, the use of PB significantly increased the rate of normokalemia (RR 2.02, 95% CI: 1.55 - 2.62; p0.001, Fig. 1B). The incidence of any adverse effects shows no statistical difference between groups (RR 1.09, 95% CI: 0.99-1.19; p=0.07, Fig. 2A), as also in serious adverse effects (RR 1.03, 95% CI: 0,82-1.30; p = 0.8, Fig. 2B) Conclusions Our study shows the effectiveness of potassium binders in reducing mean sK+ and maintaining normokalemia in patients with hyperkalemia. Treatment comparing Patiromer, SZC and placebo do not show changes in rate of adverse effects, evinced safety profile in these interventions. All these findings support the use of new potassium binders as an effectiveness and safety option to treat hyperkalemia.Efficacy of Potassium binders Safety of Potassium binders