Potassium-increasing regimens in patients at high risk of ventricular arrhythmias: a prespecified observational analysis of the randomized POTCAST trial

The POTCAST trial (n = 1200) showed that targeting high-normal plasma potassium levels reduced ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). We compared changes in plasma potassium and described outcomes across the three regimens used to increase plasma potassium.

We studied 600 control participants and 572 intervention participants who completed potassium up-titration in POTCAST. Participants in the intervention arm were categorized according to treatment after plasma-potassium up-titration into (i) mineralocorticoid-receptor antagonists (MRAs) monotherapy, (ii) potassium-supplement monotherapy, or (iii) combination therapy with both. The primary endpoint was a composite of sustained ventricular arrhythmia, appropriate ICD therapy, hospitalization for arrhythmia or heart failure, or all-cause mortality. Safety outcomes included death and electrolyte/renal disturbances.

After 6 months, plasma potassium increased from 4.12 to 4.27 mmol/L (P = 0.004) with MRA, from 3.99 to 4.24 mmol/L (P < 0.001) with potassium supplements, and from 3.98 to 4.34 mmol/L (P < 0.001) with combination therapy. The primary endpoint occurred in 29% (n = 175) of controls, 22% (n = 16) in the MRA group, 21% (n = 31) in the potassium supplements group, and 22% (n = 72) in the combination therapy group (P = 0.8 between regimens). Hypokalemia occurred in 13% of controls and in 3, 9, and 5% of participants receiving MRA, potassium supplements, and combination therapy, respectively. Hyperkalemia occurred in 0.2% of controls and in 0, 3, and 4% of participants receiving MRA, potassium supplements, and combination therapy (P > 0.1 between regimens).

Treatment with MRA, potassium supplements, or both increased potassium levels. All regimens were associated with numerically lower endpoint rates than controls. We detected no statistically significant differences in endpoints or safety between regimens.