Decreased Arrhythmia Burden in High-Risk CVD With Targeted Potassium Levels

ventricular arrhythmia
ventricular arrhythmia
Researchers sought to determine if increased plasma potassium concentration decreases risk for malignant arrhythmia in high-risk patients with CVD.

The use of easily available treatments to increase low plasma potassium levels has been suggested as a new therapeutic strategy to decrease the burden of arrhythmia in high-risk patients with cardiovascular disease (CVD). These interim findings were published in the American Heart Journal.

The prospective, randomized, open-label POTCAST trial ( Identifier: NCT03833089) is being conducted to explore whether high-normal potassium levels (defined as 4.5-5.0 mmol/L) reduce the risk for malignant cardiac arrhythmias and all-cause death among high-risk patients with a CVD and an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Additionally, the investigators aim to examine whether high-normal potassium levels can be attained safely and maintained with the use of already available oral potassium supplements and mineralocorticoid receptor antagonists, along with potassium-rich dietary guidance.

The primary endpoint of POTCAST is a composite of electrocardiogram-documented ventricular tachycardia of more than 125 beats per minute that last for 30 seconds or longer; any appropriate ICD treatment, as documented by ICD interrogations; and all-cause death.

Based on calculations of sample size, it is estimated that 1000 patients will be randomly assigned in a 1:1 ratio to receive either an investigational regimen, which is intended to increase/maintain potassium at high-normal levels, or to usual care. All patients will be followed for approximately 4 years. The study will continue until a total of 291 events have occurred, thus providing an α=0.05 and a 1-β=0.80.

The trial is enrolling participants from 3 sites in Denmark: Copenhagen University Hospital in Rigshospitalet, Copenhagen University Hospital in Herlev and Gentofte, and Zealand University Hospital in Roskilde. All of these study sites have active ICD clinics for screening and enrolling patients. The study will enroll patients with an indication for ICD implantation, regardless of the cause and the a person’s diagnosis.

All patients are screened with a blood test. If the test results show a potassium level of 4.3 mmol/L or less, those individuals will then be randomly assigned in a 1:1 ratio via a concealed computer-generated sequence. Prior to randomization, all participants will have their medical treatment reviewed to ensure that it adheres to national guideline-recommended treatment of the disease for which the ICD has been implanted.

As of March 31, 2022, a total of 739 participants have been included in the study. Enrollment is anticipated to be completed by the end of 2022. Follow-up will conclude when the desired number of individuals have met the primary endpoint. After this, 1 year is permitted for data analysis. Publication of the main study is estimated to occur in 2024.

“The POTCAST trial will be the first study to investigate whether stabilizing plasma potassium at high-normal therapeutic levels can be done safely with the use of mineralocorticoid antagonists, oral potassium supplementation and dietary guidance, and if this can prevent ventricular arrhythmia and improve survival as a general strategy for all-comer ICD treated patients,” the study authors wrote.

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.


Winsløw U, Sakthivel T, Zheng C, et al. Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST); study protocol for a randomized controlled trial. Am Heart J. Published online July 11, 2022. doi:10.1016/j.ahj.2022.07.003