Physicians' Academy for Cardiovascular Education

Hyperkalemia in new-onset HFrEF patients receiving guideline-directed medical therapies

Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure

Literature - Henrysson J, Thunström E, Chen X, et al. - ESC Heart Fail. 2022 Sep 25 [Online ahead of print]. doi: 10.1002/ehf2.14137

Introduction and methods


Despite improvement in the treatment of patients with HFrEF, the 5-year survival rate after hospitalization in this group is still only 25% [1]. One of the underlying reasons is suboptimal clinical implementation of guideline-directed medical therapies (GDMTs), such as MRAs. Although the 2016 ESC Guidelines on HF recommend MRAs as part of the first-line therapy for HFrEF patients [2], these drugs are often not prescribed, underdosed, or discontinued due to adverse events [3-6].

Potential reasons for the underuse of MRAs are hyperkalemia and worsening renal function [7,8]. However, the reported incidence of hyperkalemia in MRA-treated patients varies and is too low to explain the proportion of undertreated patients.

Aim of the study

The study aim was to investigate the incidence and magnitude of documented hyperkalemia and the expected risk of hyperkalemia in HFrEF patients at baseline (i.e., time of HFrEF diagnosis) and during optimal uptitration of GDMTs in a real-world setting.


This was a retrospective observational analysis of the medical records of 630 patients who had been hospitalized for new-onset HFrEF at the Sahlgrenska University Hospital in Gothenburg, Sweden from January 2016 through December 2019. The study was conducted in the fall of 2020 (mean observation time: 13.4 months; SD: 29.12). During the study period, potassium binders were not used in clinical practice at the three hospitals affiliated with the Sahlgrenska University Hospital.

According to the 2016 ESC Guidelines, all newly diagnosed HFrEF patients must go through maximum uptitration of ACEi/ARB beta-blocker, and MRA within 6 months after the diagnosis [2]. Therefore, study patients were divided into 4 groups based on potentially receiving MRA treatment within the first 6 months: (1) those who never received an MRA, (2) those who needed an MRA dose reduction, (3) those who needed MRA discontinuation, and (4) those on stable MRA treatment. Potassium levels (in serum or plasma) were assessed at baseline, and the highest potassium level during the 6 months after baseline was also recorded. The expected risk of hyperkalemia included an overall assessment based on previous studies [9].

In an exploratory analysis, all-cause mortality of patients not treated with MRA was compared with that of matched (for age, sex, and comorbidities) patients treated with MRA from the Swedish Heart Failure Registry, a nationwide HF registry implemented in Sweden in 2003 [10].

Main results

Incidence of documented hyperkalemia and expected hyperkalemia risk at baseline and follow-up

//Hypokalemia/normokalemia at baseline and hyperkalemia at follow-up//

//Exploratory analysis of all-cause mortality after 1 year//


In a retrospective analysis of an observational cohort, the incidence of hyperkalemia increased from 6% at the time of the HFrEF diagnosis to 24% during uptitration of GDMTs in 6 months. During this time, the expected risk of hyperkalemia increased 2.7-fold. However, after the 6 months, less than 50% of the HFrEF patients were on MRA treatment. The incidence and magnitude of hyperkalemia did vary considerably between different clinical phenotypes.

Based on their results, the authors believe that physicians might be reluctant to prescribe MRAs to HFrEF patients when they believe the hyperkalemia risk is high based on their clinical experience. “Our data should help clinicians estimate the ‘real and potential’ risk of hyperkalemia and, most importantly, provide tailored therapy to HF patients by treating them with GDMT while preventing hyperkalemia, either by increasing the use of ARNI and SGLT2 inhibitors, which may moderate the risk of hyperkalemia, or by adding a potassium binder in those with a higher risk of hyperkalemia.”


Show references

Find this article online at ESC Heart Fail.

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