A strategy of actively increasing plasma potassium to high-normal levels significantly lowered the risk of arrhythmia events in high-risk patients with an implantable cardioverter–defibrillator (ICD), according to results from the POTCAST trial.¹˒² The findings were presented at the European Society of Cardiology (ESC) Congress 2025 and simultaneously published in the New England Journal of Medicine.¹

POTCAST was a multicentre, open-label, randomised superiority trial conducted in Denmark. It enrolled 1200 participants with an ICD who were at high risk for ventricular arrhythmias and had a baseline plasma potassium level of ≤4.3 mmol/L. Participants were assigned 1:1 to either an intervention group, which aimed to increase and maintain plasma potassium at a high-normal level (4.5–5.0 mmol/L) using potassium supplements, a mineralocorticoid receptor antagonist, or both, plus dietary guidance, or to a standard care group. The primary endpoint was a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalisation for arrhythmia or heart failure, or death from any cause.

Over a median follow-up of 39.6 months, the intervention resulted in a mean increase in plasma potassium of approximately 0.3 mmol/L. A primary endpoint event occurred in 136 participants (22.7%) in the high-normal potassium group compared with 175 participants (29.2%) in the standard care group, corresponding to a 24% lower risk (hazard ratio, 0.76; 95% confidence interval, 0.61–0.95; P=0.01). This result was primarily driven by a 25% reduction in ventricular tachycardia. The incidence of hospitalisation for hyperkalemia or hypokalemia was similar between the two groups.

The trial provides randomised evidence supporting the management of potassium levels in this high-risk population. The study authors concluded that, "Among participants with any cardiovascular disease who had an ICD and were at high risk for ventricular arrhythmias, a treatment-induced increase in plasma potassium levels led to a significantly lower risk of appropriate ICD therapy, unplanned hospitalisation for arrhythmia or heart failure, or death from any cause than standard care."¹ Commenting on the findings, Dr Theresa McDonagh of King's College Hospital, London, UK, noted the importance of aiming for higher potassium levels "without obviously going into the toxic range," adding, "I think they found a good sweet spot."²

While the results are directly applicable to patients with ICDs, the investigators suggest the benefits of higher potassium intake could potentially extend to a broader population of patients with cardiovascular disease.²

This study was funded by the Independent Research Fund Denmark, the Novo Nordisk Foundation, and the Danish Heart Foundation.

References

1. Jøns C, Zheng C, Winsløw UCG, et al. Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias. N Engl J Med. 2025. https://doi.org/10.1056/NEJMoa2509542.

2. Hughes S. Raising Potassium Cuts Arrhythmias in ICD Patients. Medscape. 29 August 2025. https://www.medscape.com/viewarticle/raising-potassium-cuts-arrhythmias-icd-patients-2025a1000mx2.

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