Internal medicine

Organic chemistry

Hazard ratio

Empagliflozin

Heart failure

Discontinuation

Hyperkalemia

Population

Potassium

Diabetes mellitus

Ejection fraction

Gastroenterology

Endocrinology

Cardiology

Chemistry

Type 2 diabetes

Spironolactone

Confidence interval

Medicine

Environmental health

European Heart Journal

Aims Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen heart failure prognosis. Some studies suggested that sodium-glucose cotransporter 2 inhibitors reduce hyperkalaemia, an effect that may have important clinical implications. This analysis evaluates the effect of empagliflozin on the occurrence of hyper- and hypokalaemia in HF. Methods and results EMPEROR-Pooled (i.e. EMPEROR-Reduced and EMPEROR-Preserved combined) included 9583 patients with available serum potassium levels at baseline (98.6% of the total EMPEROR-Pooled population, n = 9718). Hyperkalaemia was identified by investigators’ reports of adverse events, and by a laboratory serum potassium value above 5.5 mmol/L and 6.0 mmol/L. The main outcome was a composite of investigator-reported hyperkalaemia or initiation of potassium binders. 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 (compared with placebo) reduced the composite of investigator-reported hyperkalaemia or initiation of potassium binders [6.5% vs. 7.7%, hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71–0.95, P = 0.01]. Empagliflozin reduced hyperkalaemia rates regardless of the definition used (serum potassium &amp;gt;5.5 mmol/l: 8.6% vs. 9.9%, HR 0.85, 95% CI 0.74–0.97, P = 0.017; serum potassium &amp;gt;6.0 mmol/l: 1.9% vs. 2.9%, HR 0.62, 95% CI 0.48–0.81, P &amp;lt; 0.001). The incidence of hypokalaemia (investigator-reported or serum potassium &amp;lt;3.0 mmol/l) was not significantly increased with empagliflozin. Conclusions Empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.

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