EvidenceAlerts

Ferreira JP, Zannad F, Butler J, et al. Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled. Eur Heart J. 2022 Jun 10. pii: 6605266. doi: 10.1093/eurheartj/ehac306. (Original study)
Abstract

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 >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.

CONCLUSIONS: Empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.

Ratings
Discipline Area Score
Internal Medicine 6 / 7
Cardiology 5 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Comments from MORE raters

Cardiology rater

Really interesting paper showing another benefit of SGLT2i in patient with HF. Along with the evidence of Entresto reducing the rate of hyperK, this article reminds us that foundational therapies for HF not only potentiate each other, but also protect patients from adverse events that might limit the medication dosage.

Family Medicine (FM)/General Practice (GP) rater

The SGLT2 inhibitors have already found their way into daily practice, including primary care. This study explores one of the important safety issues and the results give additional support to empagliflozin in some HF patients.

Internal Medicine rater

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. Empagliflozin reduced the incidence of hyperkalaemia without a significant increase in hypokalemia in HFpEF and HFrEF.
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