Increasing the Potassium Level in Patients at High Risk for Ventricular Arrhythmias

Hypokalemia and even low-normal plasma potassium levels increase the risk of ventricular arrhythmias among patients with cardiovascular disease. An assessment of a strategy of actively increasing plasma potassium levels to the high-normal range is needed. In this multicenter, open-label, event-driven, randomized superiority trial conducted in Denmark, we enrolled participants at high risk for ventricular arrhythmias (defined as those with an implantable cardioverter-defibrillator ICD) and with a baseline plasma potassium level of 4.3 mmol per liter or lower. Participants were randomly assigned, in a 1:1 ratio, to a treatment regimen aimed at increasing the plasma potassium level to a high-normal level (4.5 to 5.0 mmol per liter) by means of potassium supplementation, a mineralocorticoid receptor antagonist, or both plus dietary guidance and standard care (high-normal potassium group) or to standard care only (standard-care group). The primary end point was a composite of documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization (>24 hours) for arrhythmia or heart failure, or death from any cause, assessed in a time-to-first-event analysis. Among the 1200 participants who underwent randomization (600 assigned to each group), the median duration of follow-up was 39.6 months (interquartile range, 26.4 to 49.3). A primary end-point event occurred in 136 participants (22.7%; 7.3 events per 100 person-years) in the high-normal potassium group, as compared with 175 participants (29.2%; 9.6 events per 100 person-years) in the standard-care group (hazard ratio, 0.76; 95% confidence interval, 0.61 to 0.95; P = 0.01). The incidence of hospitalization for hyperkalemia or hypokalemia was similar in the two groups. Among participants with any cardiovascular disease who had an ICD and were at high risk for ventricular arrhythmias, 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. (Funded by the Independent Research Fund Denmark and others; POTCAST ClinicalTrials.gov number, NCT03833089.).