Empagliflozin effectively regulates Serum potassium in Heart Failure, study

France: Empagliflozin (anti-diabetic medication) reduced the incidence of hyperkalemia without a substantial increase in hypokalemia in patients with heart failure (HF) across the full range of ejection fraction, states analysis data published in the European Heart Journal.

Potassium is the most abundant cation in the intracellular fluid and it plays a vital role in the maintenance of normal cell functions. Severe potassium abnormalities can lead to cardiac arrhythmias and death. Dyskalemia (hypo- and hyperkalemia) is associated with poor prognosis in HF. Hyperkalaemia frequently leads to the interruption and discontinuation of neurohormonal antagonists, which may further worsen the prognosis of heart failure. Some studies have suggested that sodium-glucose cotransporter 2 inhibitors like Empagliflozin reduce hyperkalaemia, an effect that may have important clinical implications.

A team of investigators conducted a study analysis to evaluate the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF in EMPEROR-Reduced and EMPEROR-Preserved combined.

EMPEROR-Pooled included 9583 patients with baseline serum potassium levels (98.6% of total EMPEROR-Pooled population, n = 9718). Hyperkalemia was identified by investigators' reports of adverse events and by laboratory serum potassium >5.5 mmol/l or >6.0 mmol/l. The primary outcome was a composite of time-to-first HF hospitalization (HHF) or cardiovascular death. Investigators used Descriptive statistics and Cox models.

Key findings of the study are,

• Patients with high potassium at baseline were more frequently diagnosed with diabetes and ischaemic HF aetiology and had lower left ventricular ejection fraction and estimated glomerular filtration rate but were more frequently treated with sacubitril/valsartan or mineralocorticoid receptor antagonists.

• Empagliflozin reduced the composite of investigator-reported hyperkalaemia or initiation potassium binders, compared with the placebo

• Empagliflozin reduced hyperkalaemia rates regardless of the definition used (serum potassium >5.5 mmol/l: 8.6% vs. 9.9%, HR 0.85, 95% CI 0.74–0.97, P = 0.017; serum potassium >6.0 mmol/l: 1.9% vs. 2.9%, HR 0.62, 95% CI 0.48–0.81, P < 0.001).

• The incidence of hypokalaemia (investigator-reported or serum potassium <3.0 mmol/l) was not significantly increased with empagliflozin.

From the study data, the investigators conclude that both hyper- and hypokalemia are associated with worse outcomes. Empagliflozin (vs. placebo) reduced the rate of new-onset hyperkalaemia or new initiation of potassium binders without increasing the incidence of hypokalaemia in a significant manner.

The study findings are clinically important and expand the potential benefits of Empagliflozin in HF, the authors wrote.

João Pedro Ferreira, Faiez Zannad, Javed Butler, Gerasimos Filipattos, Ivana Ritter, Elke Schüler, Bettina J Kraus, Stuart J. Pocock, Stefan D. Anker, Milton Packer, Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled, European Heart Journal, 2022, ehac306, https://doi.org/10.1093/eurheartj/ehac306