A randomized clinical trial in Denmark found that increasing plasma potassium levels to the high-normal range lowered the risk of adverse outcomes in patients with implantable cardioverter-defibrillators , according to late-breaking research presented in a Hot Line session at ESC Congress 2025 and simultaneously published in New England Journal of Medicine.
Over a median follow-up of nearly 40 months, 23% of patients in the high-normal potassium group reached the primary composite outcome vs 29% in the standard care group. This corresponded to event rates of 7 vs 10 per 100 person-years. “A treatment-induced increase in plasma potassium levels led to a significantly lower risk of appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause than standard care,” said Christian Jøns, M.D., Ph.D. from the Department of Cardiology, Institute for Clinical Medicine, University of Copenhagen, Copenhagen, and colleagues.
The composite outcome included sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillators (ICD) therapy, unplanned hospitalization for arrhythmia or heart failure, or death from any cause. ICD therapy or ventricular tachycardia occurred in 15% of patients in the intervention group vs 20% with standard care. Arrhythmia-related hospitalizations were 7% vs 11%, heart failure hospitalizations were less frequent, and deaths were reported in 6% vs 7%.
The POTCAST trial enrolled 1,200 patients with baseline potassium levels of 4.3 mmol/L or less. Participants were randomized to a regimen targeting potassium levels between 4.5 and 5.0 mmol/L or to standard care. Treatment included potassium supplements, mineralocorticoid receptor antagonists, and dietary counseling, adjusted through frequent visits until potassium levels stabilized. At nearly 3 months, mean potassium increased from 4.0 mmol/L at baseline to 4.4 mmol/L in the intervention group, while levels in the standard care group remained unchanged. About 44% of treated patients reached the full target range.
Safety monitoring showed no treatment-related deaths. Hospitalizations due to hypokalemia, hyperkalemia, or kidney failure occurred in 17 patients in the intervention group and 10 patients in the control group. Mean plasma creatinine was modestly higher in the intervention group, with a hazard ratio of 1.75 for electrolyte/kidney-related hospitalizations.
Participants had a mean age of 63 years, and nearly 20% were women. Nearly two-thirds (65%) had a history of heart failure, and 43% received ICDs for primary prevention. Subgroup analyses showed consistent results across age, sex, baseline potassium, heart failure status, and device type.
Limitations included the Denmark-only population, inclusion limited to patients with ICDs or cardiac-resynchronization therapy defibrillator devices (excluding those without such devices), unmeasured adherence to dietary guidance, and some diagnostic subgroups were small. The open-label design could have introduced bias, although all outcomes were adjudicated by an independent blinded committee.
Full disclosure can be found in the study.
