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

OBJECTIVE

Hyperkalemia is a potentially life-threatening electrolyte imbalance that contributes to increased morbidity and mortality in patients with heart failure (HF) and chronic kidney disease (CKD). Novel potassium binders (NPBs) have been shown to prevent hyperkalemia; however, their efficacy and safety have not been fully established.

METHODS

We searched various electronic databases, including MEDLINE (via PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov, to retrieve randomized controlled trials comparing NPB to placebo in patients with chronic hyperkalemia due to HF or CKD.

RESULTS

Our meta-analysis, including 12 studies involving 2517 patients, showed that NPBs, including patiromer and sodium zirconium cyclosilicate, were associated with significant mineralocorticoid receptor antagonist (MRA) optimization (relative risk [RR]: 1.28; 95% confidence interval [CI]: 1.14-1.43) as compared to placebo. The results were consistent for subgroups of sodium zirconium cyclosilicate, patiromer, CKD, and HF. NPBs also significantly reduced the incidence of hyperkalemia (RR: 0.37; 95% CI: 0.22-0.6). Additionally, NPBs reduced the mean serum potassium level from baseline as compared to placebo (mean difference: -0.46; 95% CI: -0.77 to -0.15) and MRA optimization at less than the target dose (RR: 0.62; 95% CI: 0.42-0.85). The risk of adverse events, serious adverse events, and all-cause mortality remained comparable between the two groups.

CONCLUSION

This meta-analysis highlights the potential of NPBs to facilitate MRA optimization, reduce hyperkalemic episodes, and maintain serum potassium levels in patients with hyperkalemia, without a corresponding increase in adverse events. However, further research through large-scale studies is needed to confirm the sustained clinical benefits of NPBs, establish standardized treatment protocols, and evaluate their effectiveness across diverse patient populations with CKD and HF.