Increasing potassium levels improve cardiac outcomes

Targeting high-normal potassium levels reduced the risk of arrhythmias, hospitalisation for heart failure or arrhythmia and death compared with no intervention, according to research on the POTCAST trial presented at ESC Congress 2025. 

“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. 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 implantable cardioverter defibrillator (ICD),” Dr Christian Jons, Rigshospitalet – Copenhagen University Hospital, Denmark, explained.

The open label randomised controlled trial was conducted at three sites in Denmark. Eligible participants had an ICD or cardiac resynchronisation therapy defibrillator and had a baseline plasma potassium ≤4.3mmol/L. Exclusion criteria included renal impairment (eGFR <30mL per minute per 1.73m²) and pregnancy.  

Participants were randomised 1:1 to a treatment regimen aiming at increasing plasma potassium levels to 4.5-5.0mmol/L, using dietary guidance, potassium supplements and/or mineralocorticoid receptor antagonist (MRA) therapy, or to standard care. The primary endpoint was a composite of sustained ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD therapy, unplanned hospitalisation (>24 hours) due to arrhythmia or heart failure, and all-cause mortality. 

Among 1,200 participants who had undergone randomisation, median follow-up was 39.6 months. The mean age of the participants was 62.7 years and 19.8 per cent were women. From mean baseline levels of 4.01mmol/L, plasma potassium levels reached a mean of 4.36mmol/L in the high-normal potassium group compared with 4.05mmol/L in the control group after six months. 

The primary endpoint was significantly lower in the high-normal potassium group (22.7%) than in the control group (29.2%; hazard ratio [HR] 0.76; 95% CI 0.61 to 0.95; p=0.015). The effect was consistent across prespecified subgroups, including ischaemic heart disease and heart failure. 

Any appropriate ICD therapy (shock therapy or anti-tachycardia pacing) was the main driver of the difference, occurring in 15.3 per cent of participants in the high-normal potassium group and 20.3 per cent in the control group (HR 0.75; 95% CI 0.57 to 0.80). Unplanned hospitalisations for cardiac arrhythmias occurred in 6.7 per cent of participants in the high-normal group and 10.7 per cent in the control group (HR 0.63; 95% CI 0.28 to 0.64). Unplanned hospitalisations for heart failure occurred in 3.5 and 5.5 per cent participants, respectively (HR 0.62; 95% CI 0.37 to 1.11). A total of 5.7 per cent in the high-normal potassium group and 6.8 per cent in the control group died (HR 0.85; 95% CI 0.54 to 1.34).  

Regarding safety outcomes, hospitalisation due to very high (hyperkalaemia) or very low (hypokalaemia) potassium levels occurred in 1 per cent of participants in both groups. An unplanned hospitalisation lasting more than 24 hours and death from all causes occurred in 29.5 per cent of participants in the high-normal potassium group and 33.2 per cent in the control group (HR 0.88; 95% CI 0.72 to 1.08). 

Summing up, Prof Henning Bundgaard, senior author, said: “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.

“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 cardi- ovascular diseases associated with a high risk of ventricular arrhythmia.”