Hyper- and hypokalemia in patients with heart failure (HF) are associated with an increased risk for death, new research suggests.

In a retrospective study of 21,334 patients with newly diagnosed HF in the United Kingdom, more than half experienced episodes of out of range serum potassium levels: 9.2%, 35.9%, 12.8%, and 3.6% had serum potassium values less than 3.5, 5.0 or higher, 5.5 or higher, and 6.0 mmol/L or higher, respectively. By design, no patients had chronic kidney disease (CKD, estimated glomerular filtration rate less than 60 mL/min/1.73 m2) or required dialysis prior to the study (although they could have developed CKD afterward).

Phil McEwan, PhD, of Health Economics and Outcomes Research in the United Kingdom, and colleagues observed a significant U-shaped curve between serum potassium levels and all-cause mortality. Compared with normal potassium values of 4.5 to less than 5.0 mmol/L (reference), serum potassium values less than 3.5, 5.0 to less than 5.5, 5.5 to less than 6.0, and more than 6.0 mmol/L were associated with a significant 2-,  1.2-, 1.3-, and 3-fold higher risk for death, respectively, according to results published in ESC Heart Failure. The findings for major adverse cardiac events were nonsignificant.

The team also found that hyperkalemia increased the risk of discontinuing therapy with renin–angiotensin–aldosterone system inhibitors (RAASi). Compared with the reference category, potassium levels of 5.5 to less than 6.0 and more than 6.0 mmol/L were associated with a significant 1.3- and 2.1-fold increased risk for RAASi discontinuation, respectively. The investigators did not know whether RAASi was discontinued due to increased creatinine levels, serum potassium change, or both.

“Our results demonstrate the potential importance of serum potassium in HF outcomes and management,” Dr McEwan and peers stated. “Further work is needed to explore whether potassium itself causes adverse outcomes or is a marker of higher risk.”

To prevent hyperkalemia, the team emphasized monitoring of potassium intake, laboratory surveillance, and physician awareness of drug interactions. They noted that novel potassium-binding agents might also help.

The study was funded by AstraZeneca, the producers of Lokelma (sodium zirconium cyclosilicate).

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Linde C, Qin L, Bakhai A, et al. Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK. ESC Heart Failure 2019; 6:280–290