Hypokalaemia and low-normal plasma potassium levels are known to increase the risk of ventricular arrhythmias in patients with cardiovascular disease. A new study has assessed a strategy of actively increasing plasma potassium to the high-normal range to mitigate this risk in a high-risk population.¹
The POTCAST trial (NCT03833089) was a multicentre, open-label, event-driven, randomised superiority trial conducted in Denmark. The study enrolled 1,200 participants at high risk for ventricular arrhythmias, defined as those with an implantable cardioverter–defibrillator (ICD), and a baseline plasma potassium level of 4.3 mmol per litre or lower.¹
Participants were randomly assigned in a 1:1 ratio to either a high-normal potassium group or a standard-care group. The intervention group received a treatment regimen aimed at increasing and maintaining the plasma potassium level to a high-normal level (4.5 to 5.0 mmol per litre). This was achieved through potassium supplementation, a mineralocorticoid receptor antagonist, or both, in addition to dietary guidance and standard care. The control group received standard care only.
The primary endpoint was a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalisation (>24 hours) for arrhythmia or heart failure, or death from any cause, assessed in a time-to-first-event analysis.
Over a median follow-up of 39.6 months, a primary endpoint event occurred in 136 of 600 participants (22.7%) in the high-normal potassium group, corresponding to 7.3 events per 100 person-years. In the standard-care group, 175 of 600 participants (29.2%) experienced a primary endpoint event, corresponding to 9.6 events per 100 person-years (hazard ratio, 0.76; 95% confidence interval, 0.61 to 0.95; P=0.01).¹
The incidence of hospitalisation for hyperkalaemia or hypokalaemia was reported to be similar between the two groups, indicating a favourable safety profile for the intervention.
These findings suggest that for patients with cardiovascular disease and an ICD, actively managing potassium levels towards the high-normal range can significantly reduce major arrhythmic and heart failure events. According to the POTCAST Study Group, among these high-risk participants, “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 This strategy could be a valuable addition to the management of patients at high risk for ventricular arrhythmias.²
This study was funded by the Independent Research Fund Denmark, the Novo Nordisk Foundation, and the Danish Heart Foundation.
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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;393:1979-1989. https://doi.org/10.1056/NEJMoa2509542
2. Chatterjee NA. Targeting Potassium for Prevention of Ventricular Arrhythmias. N Engl J Med 2025;393:2047-2048. https://doi.org/10.1056/NEJMe2513662