A treatment-induced increase in plasma potassium levels reduced the risk of ventricular arrhythmias, in patients with ICDs and baseline plasma potassium levels of 4.3 mmol per liter or lower, based on findings from the POTCAST Trial presented at ESC Congress 2025 and simultaneously published in NEJM. This targeting of high-normal potassium levels also reduced unplanned hospitalizations for arrhythmia or heart failure, as well as death from any cause compared with standard care.

"There is some evidence from observational studies to suggest that low plasma potassium levels are associated with increased risk of dangerous alterations in heart rhythms and that potassium levels in the upper normal level have protective effects," said Christian Jons, MD, who presented the findings. "We conducted the POTCAST trial to assess the benefits and risks of targeting high-normal potassium levels in patients at high risk of ventricular arrhythmias with an ICD."

Jons and colleagues randomly assigned 1,200 patients from three sites in Denmark (mean age was approximately 63 years and nearly 20% were women) to either standard care or a treatment regimen designed to increase plasma potassium levels to high-normal (4.5 to 5.0 mmol per liter) that included potassium supplementation, a mineralocorticoid receptor antagonist, or both, plus dietary guidance and standard care. Median follow-up was 39.6 months.

Overall results showed a significantly lower risk of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause in the high-normal potassium cohort compared with the standard care cohort (22.7% vs. 29.2%, respectively). Researchers noted the effect was consistent across prespecified subgroups, including participants with ischemic heart disease and heart failure. They also added that any appropriate ICD therapy, such as shock therapy or anti-tachycardia pacing, was the primary cause of the difference between the two groups, occurring in 15.3% of patients in the high-normal potassium group and 20.3% of those in the standard care group.

In other findings, hospitalization due to hyperkalemia or hypokalemia potassium levels occurred in 1% of participants in both groups. Unplanned hospitalizations lasting more than 24 hours and death from all causes occurred in 29.5% of participants in the high-normal potassium group compared with 33.2% in the standard care group.

"The findings of POTCAST lead us to speculate that increased potassium levels may, at least partially, be responsible for MRAs' positive outcomes, rather than merely being a side effect," said senior author Henning Bundgaard, MD. "We believe the time is right to consider increasing potassium levels to the mid-to-high normal range as an inexpensive and widely available treatment strategy in patients with a broad spectrum of cardiovascular diseases associated with a high risk of ventricular arrhythmia."