Boosting potassium wards off ventricular arrhythmias in patients with ICD

Increasing low potassium levels improves clinical outcomes in patients with cardiovascular disease (CVD) and a high risk for ventricular arrhythmias, as shown in the POTCAST trial presented at ESC 2025.

Over a median follow-up of 39.6 months, patients who had their potassium levels boosted had a lower rate of the composite endpoint* (22.7 percent vs 29.2 percent; hazard ratio [HR], 0.76). The effects were consistent across various subgroups, including those who received or did not receive MRAs at the end of the adjustment period, as well as those who achieved or did not achieve their plasma potassium target. [N Engl J Med 2025;doi:10.1056/NEJMoa2509542]

The difference between groups was primarily due to reductions in appropriate implantable cardioverter-defibrillator (ICD) therapy or documented ventricular tachycardia (15.3 percent vs 20.3 percent; HR, 0.75) and unplanned hospitalizations for cardiac arrhythmias (6.7 percent vs 10.7 percent; HR, 0.63).

There were no significant differences in unplanned hospitalizations for heart failure (3.5 percent vs 5.5 percent; HR, 0.64) or all-cause death (5.7 percent vs 6.8 percent; HR, 0.85).

In terms of safety, there was no significant difference in the number of hospitalizations for hyperkalaemia, hypokalaemia, or kidney failure between the intervention and control groups (17 vs 12; HR, 1.75).

POTCAST population

The POTCAST study was conducted across three clinics in Denmark. It included 1,200 ICD recipients (mean age 62.7 years, 19.8 percent women) with a baseline plasma potassium level of ≤4.3 mmol/L. Most patients (64.6 percent) had a history of heart failure, half had a history of ischaemic heart disease, whereas the other half had cardiomyopathies or primary arrhythmia disorders. ICDs had been implanted for primary prevention in 43.3 percent of the group.

Patients were randomly assigned to receive either potassium treatment or usual care alone. At baseline, the mean potassium level was 4.01 mmol/L in both groups. This was increased to 4.36 mmol/L in the intervention group and to 4.05 mmol/L in the usual care group. Clinical events were analysed after a median follow-up of 39.6 months.

To achieve this, patients were started on mineralocorticoid receptor antagonists and/or potassium supplements, with dietary guidance, while the current use of potassium-losing diuretics was reduced or discontinued. The uptitration period lasted 85 days.

Not a novel idea

The link between low (or low-normal) potassium and ventricular arrhythmias is not a new concept.

“For years, we have been teaching cardiologists in training to target potassium above 4 [mmol/L],” said ESC session panelist Dr Isabelle Van Gelder from University Medical Centre Groningen in the Netherlands.

Too much potassium, however, is known to pose a risk to certain groups, such as people with severely impaired kidney function. What the POTCAST investigators achieved was a “good, sweet spot,” commented fellow panelist Dr Theresa McDonagh of King’s College London. “It's important to hear this message to allow potassium to go as high as possible without entering the toxic range.”

When asked whether the results could apply to other patient groups, study investigator Dr Christian Jøns from Rigshospitalet – Copenhagen University Hospital, Denmark, said the trial included a large proportion of patients with primary prevention indications for ICD placement and those with normal ejection fractions. “With that in mind, I think we can extend [the findings] to a greater proportion of our cardiovascular patients.”