Clinical question: Does a treatment strategy targeting high-normal plasma potassium levels (4.5 to 5.0 mmol/L) reduce the risk of ventricular arrhythmias and cardiovascular events in high-risk patients with implantable cardioverter-defibrillators (ICDs)?
Background: Low, or even low-normal, potassium levels are associated with increased ventricular arrhythmia risk in patients with cardiovascular disease, and prior heart failure trials suggest that therapies that raise potassium levels may have a protective effect. However, current guidelines focus primarily on avoiding hypokalemia rather than actively targeting higher potassium levels, and the benefit of intentionally increasing potassium into the high-normal range has not been well studied.
Study design: Multicenter, open-label, event-driven, randomized superiority trial
Setting: Three cardiac centers in Denmark
Synopsis: The POTCAST trial randomized 1,200 adults with an ICD and baseline plasma potassium up to 4.3 mmol/L to either a “high-normal potassium” strategy or standard care. The intervention group received potassium supplementation and/or mineralocorticoid receptor antagonists along with dietary guidance to target a potassium level of 4.5 to 5.0 mmol/L. Over a median follow-up of 39.6 months, the primary composite endpoint (sustained ventricular tachycardia, appropriate ICD therapy, unplanned hospitalization for arrhythmia or heart failure, or death) occurred in 22.7% of the intervention group compared to 29.2% in the standard care group (hazard ratio, 0.76; 95% CI, 0.61 to 0.95) with appropriate ICD therapy, documented ventricular tachycardia, and hospitalization for arrythmia accounting for the majority of events. Rates of hospitalization for hypokalemia and hyperkalemia were similar between the two groups. Limitations include an open-label design, restriction to patients with ICDs, exclusion of patients with eGFR under 30, and the homogenous Danish study population, which may limit generalizability.
Bottom line: Actively targeting high-normal plasma potassium levels may significantly reduce the risk of malignant arrhythmias and related hospitalizations in high-risk patients with ICDs.
Citation: Jøns C, et al; POTCAST study group. 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.
Dr. Rotenberg is a staff hospitalist in the department of hospital medicine at the Cleveland Clinic and clinical assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, both in Cleveland.