The open-label, randomized POTCAST study was conducted at three centres in Denmark. Participants included patients with an ICD and a baseline potassium level ≤4.3 mmol/L. Exclusion criteria included renal impairment (eGFR <30 mL/min per 1.73 m2) and pregnancy. Participants were randomized 1:1 to either treatment to increase potassium levels to 4.5–5.0 mmol/L (via dietary counselling, potassium supplements, and/or mineralocorticoid receptor antagonists) or standard care (control group).
The primary endpoint was a combination of sustained ventricular tachycardia >125 bpm (lasting longer than 30 seconds), ICD therapies, unplanned hospitalizations (>24 hours) due to arrhythmia or heart failure, and all-cause mortality.
1,200 individuals (average age 62.7 years, 19.8% women) were randomized. The median follow-up was 39.6 months. Starting from a mean baseline value of 4.01 mmol/L, mean potassium levels of 4.36 mmol/L were achieved in the treatment group after 6 months, compared with 4.05 mmol/L in the control group.
The primary endpoint occurred significantly less often in the treatment group (22.7%) than in the control group (29.2%) (HR 0.76; 95% CI [0.61; 0.95] p=0.015). This effect was consistent across all predefined subgroups, including ischemic heart disease and heart failure. The main reason for the difference were ICD therapies (shock therapy/antitachycardia pacing, 15.3% vs. 20.3%; HR 0.75; 95% CI [0.57; 0.80]), fewer unplanned hospitalizations due to arrhythmias (6.7% vs. 10.7%; HR 0.63; 95% CI [0.28; 0.64]) and fewer for heart failure (3.5% vs. 5.5%; HR 0.62; 95% CI [0.37; 1.11]). Mortality was lower in the treatment group (5.7% vs. 6.8%; HR 0.85; 95% CI [0.54; 1.34]).
The safety analysis showed that hospitalizations due to hyperkalaemia or hypokalaemia occurred in 1% of individuals in both groups. Overall, unplanned hospitalizations (>24 hours) and deaths from any cause occurred in 29.5% vs. 33.2% (HR 0.88; 95% CI [0.72; 1.08]).
The POTCAST study demonstrates that adjusting potassium levels to the upper normal range significantly reduces the arrhythmia burden without increasing the combined risk of hyperkalaemia or hypokalaemia. According to the authors, optimizing potassium levels should be considered as a cost-effective and practical measure for patients with cardiovascular disease at high risk for ventricular arrhythmias.
POTCAST is one of the rare studies showing that simple, cost-effective measures can have a substantial clinical impact. Raising potassium levels to the high normal range led to significantly fewer ICD therapies and unplanned hospitalizations, with similar safety outcomes. This highlights a parameter often regarded as a minor lab value but potentially important for prognosis.
The findings parallel those from large MRA trials, where rising potassium levels where often considered unwanted side effect. POTCAST suggests that this rise may contribute to therapeutic benefit. Clinicians should no longer view potassium solely as a risk factor for hyperkalaemia, but as a therapeutic target.
In practice, ICD patients with low potassium levels should not be left untreated. Nutritional counselling or targeted potassium supplementation should be considered.
The question remains as to how transferable the Danish results are to other healthcare systems and patient groups. But the message seems clear: potassium optimization could become a new and easily implementable therapeutic measure.
