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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

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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.

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Data availability

The data underlying this article are available in the article and in Supplementary material online.

Abbreviations

ACEi:

Angiotensin-Converting Enzyme inhibitors

ARB:

Angiotensin Receptor Blockers

ARNI:

Angiotensin receptor-neprilysin inhibitors

CI:

Confidence interval

CKD:

Chronic kidney disease

Em:

Resting membrane potential

eGFR:

Estimated glomerular filtration rate (eGFR)

HF:

Heart failure

LVEF:

Left ventricular ejection fraction

MRA:

Mineralocorticoid receptor antagonist

OR:

Odds ratio

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

RAASi:

Renin–Angiotensin–Aldosterone System inhibitors

RCT:

Randomized controlled trials

RoB2:

Cochrane tool for assessing risk of bias in randomized trials

SZC:

Sodium Zirconium Cyclosilicate

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Authors and Affiliations

Authors

Contributions

PC and TV conceived and designed the study. PC, TV, and DM independently assessed the studies for possible inclusion and collected the data. PC, HO, and MT analyzed the data. PC and DM produced the first draft of the manuscript. MCPN and ACSS made general supervision and were responsible for data interpretation and writing the final version. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Ana C. Simões e Silva.

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Conflict of interest

All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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Carvalho, P.E.P., Veiga, T.M.A., Lacerda, H. et al. 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 112, 991–1002 (2023). https://doi.org/10.1007/s00392-023-02215-2

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