TOPLINE:

In patients with heart failure with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), a serum potassium concentration of 4.2-5.0 mmol/L was associated with the lowest risk for death and the first HF hospitalisation; however, hypokalaemia was linked to significantly worse outcomes, particularly in HFrEF.

METHODOLOGY:

• Researchers conducted an individual patient-level data meta-analysis of 12 randomised controlled trials to assess whether the association between serum potassium concentrations and clinical outcomes varies between HFrEF (left ventricular ejection fraction [LVEF] ≤ 40%) and HFpEF (LVEF ≥ 50%).
• The study analysed 32,346 patients from HFrEF trials (age range, 63.1-65.6 years; 72.5%-78.6% men) and 13,723 patients from HFpEF trials (age range, 72.1-72.6 years; 41.4%-48.4% men).
• Patients were categorised into the following six groups on the basis of their baseline serum potassium concentrations: < 3.5 (hypokalaemia), ≥ 3.5 to < 4.0, ≥ 4.0 to < 4.5, ≥ 4.5 to < 5.0, ≥ 5.0 to < 5.5, and ≥ 5.5 mmol/L (hyperkalaemia); those in the range of 4.0 to < 4.5 mmol/L served as the reference group.
• The primary endpoint was all-cause death. The median follow-up duration was 24.2 months for HFrEF trials and 36.8 months for HFpEF trials.

TAKEAWAY:

• Across both HF phenotypes — HFrEF and HFpEF — a serum potassium concentration of 4.2-5.0 mmol/L was associated with the lowest risk for death and the first HF hospitalisation.
• In HFrEF, serum potassium concentrations demonstrated a reverse J-shaped association with outcomes; those with hypokalaemia had a 49% higher risk for all-cause death than those in the reference group (adjusted hazard ratio, 1.49; 95% CI, 1.27-1.76).
• Hypokalaemia was also significantly associated with increased risks for cardiovascular death, sudden death, pump failure death, and first HF hospitalisation; no significant association was observed for mild hyperkalaemia (5.0-5.5 mmol/L) even after adjustment.
• In HFpEF, a shallow U-shaped association was observed between potassium concentrations and outcomes, with a relatively small variation in the risk across baseline potassium concentrations.

IN PRACTICE:

"They underscore the importance of avoiding hypokalaemia, particularly in HFrEF. A serum potassium concentration of 4.2-5.0 mmol/L appears optimal, from a safety perspective, for patients with both HFrEF and HFpEF," the researchers of the study wrote.

SOURCE:

This study was led by Ryohei Ono, University of Glasgow, Glasgow, Scotland. It was published online on May 28, 2026, in European Heart Journal.

LIMITATIONS:

As the study represented a post hoc analysis, it remained susceptible to potential residual confounding despite extensive multivariable adjustment. The analysed data were derived from selected randomised trial populations with specific inclusion and exclusion criteria, potentially limiting generalisability to the broader patients with HF in the general population. Additionally, the exclusion of patients with baseline hyperkalaemia in several trials may have led to an underestimation of the prognostic impact of severe potassium disturbances.

DISCLOSURES:

The study derived data from multiple large randomised trials funded by industry sponsors and public agencies. Several authors disclosed serving as consultants and receiving grants, personal fees, speaking honoraria, consulting fees, and speaker fees from industry and other sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.