Physicians' Academy for Cardiovascular Education

SGLT2i reduces incidence of hyperkalemia in HF patients

Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled

Literature - Ferreira JP, Zannad F, Butler J, et al. - Eur Heart J. 2022 Jun 10;ehac306. doi: 10.1093/eurheartj/ehac306

Introduction and methods


Hyperkalemia frequently leads to the interruption or discontinuation of treatment with RAAS inhibitors [1], which may worsen the prognosis of patients with HF [2-4]. The CREDENCE, DAPA-HF, and EMPEROR-Reduced trials suggest that the SGLT2 inhibitors canagliflozin, dapagliflozin and empagliflozin may reduce the incidence of hyperkalemia in patients with T2DM and CKD [5], and in patients with HFrEF using an MRA [6,7].

Aim of the study

This secondary analysis of EMPEROR-Pooled examined the effect of empagliflozin on the incidence of hyper- and hypokalemia in patients with HF.


EMPEROR-Pooled combined individual patient data from the EMPEROR-Reduced and EMPEROR-Preserved trials (n = 9583). Both trials are international, multicenter, double-blind phase 3 studies in which adult patients with chronic HF were randomized to empagliflozin 10 mg daily or placebo in addition to their usual therapy. Patients with NYHA class II-IV symptoms for 3 or more months, an elevated NT-proBNP concentration, and an LVEF ≤ 40% (EMPEROR-Reduced) or > 40% (EMPEROR-Preserved) were eligible to participate. Hyper- and hypokalemia were determined based on investigator-reported adverse events and also defined by serum potassium concentration, with > 5.5 mmol/L (‘hyperkalemia’), > 6.0 mmol/L (‘severe hyperkalemia’), and < 3.0 mmol/L (‘severe hypokalemia’) used as cut-off values.


The main outcome was a composite of the incidence of investigator-reported hyperkalemia and the new initiation of potassium binders.

Main results




In patients with HF, treatment with empagliflozin resulted in a lower incidence of hyperkalemia, compared with placebo. The percentage of patients in whom hypokalemia occurred was similar between the two groups.


Show references

Find this article online at Eur Heart J.

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