A 68-year-old man with a medical history of heart failure with reduced ejection fraction (HFrEF; 30%), type 2 diabetes mellitus, and chronic kidney disease presents to the office for evaluation and optimization of his medication regimen. He reports shortness of breath when walking up two flights of stairs.
His current medications include sacubitril/valsartan 49/51 mg BID, metoprolol succinate 100 mg daily, and spironolactone 25 mg daily.
His laboratory studies reveal creatinine level 1.3 mg/dL (estimated glomerular filtration rate 48 mL/min/1.73 m2) and potassium level 4.8 mEq/L.
A sodium-glucose cotransporter-2 inhibitor (SGLT2i) should not be started at this time due to the risk of worsening hyperkalemia in the setting of chronic kidney disease.
The correct answer is: Fiction
As opposed to angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, SGLT2i are not associated with a significant increase in potassium levels in the setting of chronic kidney disease.
In an analysis of the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, investigators found that the incidence of investigator-reported hyperkalemia or initiation of potassium binders was lower with canagliflozin than with placebo, with hazard ratio (HR) 0.78 (95% confidence interval [CI], 0.64-0.95; p = 0.014).1 The incidence of laboratory-determined hyperkaliemia was also decreased in the canagliflozin group (HR, 0.77; 95% CI, 0.61-0.98; p = 0.031), with no effect on the risk of hypokalemia.1
In those with heart failure, randomized evidence demonstrated treatment with SGLT2i was associated with a lower risk of hyperkalemia and a lower likelihood of discontinuation of mineralocorticoid-receptor antagonists.2 Thus, among individuals at risk of hyperkalemia, use of SGLT2i should not be withheld, as they may increase adherence to therapies with proven benefits in heart failure, such as spironolactone or eplerenone.
Educational grant support provided by: Boehringer Ingelheim Pharmaceuticals Inc. (BIPI) and Lilly USA, LLC (Lilly). To visit the course page for the Heart Failure & SGLT2is: The New Pillar in Care grant,click here!
Neuen BL, Oshima M, Perkovic V, et al. Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. Eur Heart J 2021;42:4891-901.
Ferreira JP, Zannad F, Butler J, et al. Empagliflozin and serum potassium in heart failure: an analysis from EMPEROR-Pooled. Eur Heart J 2022;43:2984-93.