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

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

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© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Déclaration de conflit d'intérêts

Conflict of interest: J.P.F. reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Boehringer Ingelheim, outside the submitted work. F.Z. reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer and, Cellprothera, other from CVCT, and Cardiorenal, outside the submitted work. J.B. reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave and Vifor, outside the submitted work. G.F. reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Medtronic, Vifor, Servier, Novartis, Bayer, Amgen and Boehringer Ingelheim, outside the submitted work. I.R. and B.J.K. are employees of Boehringer Ingelheim. ES is employee of mainanalytics GmbH, contracted by Boehringer Ingelheim. SJP reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Boehringer Ingelheim, outside the submitted work. S.A. reports personal fees from Boehringer Ingelheim, during the conduct of the study; grants and personal fees from Abbott Vascular, Vifor, personal fees from Bayer, Boehringer Ingelheim, Brahms GmbH, Cardiac Dimensions, Cordio, Novartis and Servier, outside the submitted work. M.P. reports personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Abbvie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Cytokinetics, Johnson & Johnson, Eli Lily & Company, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, Theravance, and Casana, outside the submitted work.