Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials

Clin Res Cardiol. 2023 Jul;112(7):991-1002. doi: 10.1007/s00392-023-02215-2. Epub 2023 May 4.

Abstract

Background: Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF.

Methods: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations.

Results: A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%).

Conclusion: The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

Keywords: Heart failure; Hyperkalemia; Patiromer; Potassium binders; Szc.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aldosterone / pharmacology
  • Aldosterone / therapeutic use
  • Angiotensins / pharmacology
  • Angiotensins / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Humans
  • Hyperkalemia* / drug therapy
  • Hyperkalemia* / etiology
  • Hypokalemia* / complications
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Potassium
  • Randomized Controlled Trials as Topic
  • Renin / pharmacology
  • Renin / therapeutic use
  • Renin-Angiotensin System

Substances

  • Potassium
  • Renin
  • Aldosterone
  • Mineralocorticoid Receptor Antagonists
  • sodium zirconium cyclosilicate
  • Angiotensins