Mount Sinai Med-Lit Review
Clinical question: Does actively increasing serum potassium to the high-normal range (4.5 to 5.0 mmol/L) reduce malignant ventricular arrhythmias, arrhythmia-related hospitalizations, or death in patients with an implantable cardioverter-defibrillator (ICD) and baseline potassium of 4.3 mmol/L or less?
Background: Hypokalemia and even low-normal potassium levels are associated with higher risks of ventricular arrhythmia and mortality in patients with cardiovascular disease. Prior evidence shows that angiotensin-converting enzyme (ACE) inhibitors, mineralocorticoid receptor antagonists, and dietary potassium reduce cardiovascular events, but no randomized trial has directly tested whether targeting high-normal potassium levels improves outcomes in high-risk patients with cardiovascular disease.
Study design: Multicenter, open-label, randomized, event-driven, superiority trial
Setting: Three ICD-implanting centers in Denmark
Synopsis: The POTCAST trial randomized 1,200 adults with an ICD and baseline potassium of 4.3 mmol/L or less to high-normal potassium targeting via dietary counseling and potassium supplements, magnetic resonance angiography therapy, or both, versus standard care. Patients were followed for a median of 39.6 months. The intervention group increased potassium from a mean of 4.01 to a mean of 4.36 mmol/L, with only 249 patients reaching the 4.5 to 5.0 target.
The primary composite endpoint included sustained ventricular tachycardia (above 125 beats per minute for more than 30 seconds), appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death. Events occurred in 22.7% of the high-normal group versus 29.2% of standard care (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.61 to 0.95). Reductions were primarily fewer appropriate ICD therapies and arrhythmia-related hospitalizations. Mortality alone was not significantly different. Rates of hyperkalemia or hypokalemia-related hospitalizations were similar between groups.
The limitations of this study are that it was an open-label design conducted only in Denmark; it excluded patients with eGFR under 30; and fewer than half of the enrolled patients achieved the target potassium.
Bottom line: The study demonstrates that avoiding low-normal and hypokalemic states, and even modestly increasing potassium, reduces malignant arrhythmias in high-risk patients. Actively increasing potassium to the high-normal range safely reduces ventricular arrhythmias and related adverse outcomes in high-risk patients with ICDs.
Citation: Jøns C, et al. Increasing the potassium level in patients at high risk for ventricular arrhythmias. N Engl J Med. 2025;393(20):1979-1989. doi:10.1056/NEJMoa2509542.
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Dr. Hermansen
Dr. Hermansen is an assistant professor of medicine and medical education, associate clerkship director for the third-year inpatient medicine clerkship, and co-director of simulation curriculum at the Icahn School of Medicine at Mount Sinai, and a core faculty member for the internal medicine residency program at The Mount Sinai Hospital, both in New York.