Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis

source extracted confidence: high 2026-04-09
#humans #hyperkalemia #renal-insufficiency-chronic #heart-failure #renin-angiotensin-system

Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis

Huang et al., 2025 | Drugs | Systematic Review

Citation

Huang Naya, Xu Yuanwen, ... Chen Wei. Novel Potassium Binders in Reduction of Hyperkalemia and Optimization of RAAS Inhibitors Treatment in Patients with Chronic Kidney Disease or Heart Failure: A Systematic Review and Meta-analysis. Drugs. 2025-Aug;85(8):1013-1031. doi:10.1007/s40265-025-02198-6

Abstract

BACKGROUND: Renin-angiotensin-aldosterone system inhibitors (RAASi) and its combination therapy are essential supportive treatments for patients with chronic kidney disease (CKD) and heart failure (HF). Hyperkalemia (HK) is the major safety concern associated with the treatments, which often leads to RAASi dose reduction or discontinuation, thereby compromising cardiovascular protective effects. Although novel potassium binders (NPBs) are recommended by current guidelines for the treatment of HK, systematic evidence is needed to guide their use in RAASi optimization and HK management. A systematic review and meta-analysis was conducted to evaluate the incidence of HK in patients with CKD or HF who received RAASi and the efficacy of NPBs in RAASi optimization. METHODS: PubMed, Medline, Embase, and the Cochrane Library were searched from January 1, 2011 to December 31, 2023. Any studies of adult patients with CKD or HF who received RAASi were included in systematic review of HK incidence and risk factors (part 1). Randomized controlled trials (RCTs) of NPBs in patients with CKD or HF were included in meta-analysis on the efficacy of novel potassium binders (NPBs) (part 2). The primary outcome was optimization of RAASi therapy with NPBs. A pooled analysis was conducted in part 1. Network meta-analyses using a random-effects model were performed in part 2. RESULTS: A total of 83 studies (24 with CKD, 54 with HF, and 5 with CKD and HF) were included in part 1 and 8 RCTs (2 with CKD, 4 with HF, and 2 with CKD and HF) were included in part 2. The pooled HK incidence was 10.7% overall at any criteria and in all patients who received RAASi. The highest incidence of HK was observed with the combination of angiotensin converting enzyme inhibitor (ACEi)/angiotensin ii receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitor (ARNi)+ mineralocorticoid receptor antagonists (MRAs) (24.4%), followed by the triple therapy ACEi/ARB/ARNi+ sodium glucose cotransporter-2 inhibitor (SGLT2i)+MRA (10.9%), and ACEi/ARB/ARNi + SGLT2i (2.2%). Novel potassium binders improved RAASi optimization by 38% compared with placebo (risk ratio, 1.38; 95% CI, 1.16-1.65). Additionally, NPBs decreased the incidence of HK by 28% and reduced the level of potassium by 0.71 mEq/L. The CKD population showed a higher optimization rate than the HF population (84% vs 29%). CONCLUSION: The RAASi treatment was associated with high prevalence of HK, especially in bigeminal and triple therapy. The NPBs were effective in RAASi optimization and HK management, especially among the CKD population.

Key Findings

A total of 83 studies (24 with CKD, 54 with HF, and 5 with CKD and HF) were included in part 1 and 8 RCTs (2 with CKD, 4 with HF, and 2 with CKD and HF) were included in part 2. The pooled HK incidence was 10.7% overall at any criteria and in all patients who received RAASi. The highest incidence of HK was observed with the combination of angiotensin converting enzyme inhibitor (ACEi)/angiotensin ii receptor blockers (ARBs)/angiotensin receptor-neprilysin inhibitor (ARNi)+ mineralocorticoid rece

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population adult patients
Sample Size 83
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Hyperkalemia
  • Renal Insufficiency, Chronic
  • Heart Failure
  • Renin-Angiotensin System
  • Potassium
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Mineralocorticoid Receptor Antagonists
  • Chelating Agents
  • Randomized Controlled Trials as Topic

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review, Network Meta-Analysis
  • Vertical: potassium

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09