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Evevident
Original paper
2025NEJMCardiology

POTCAST

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

RCTVentricular arrhythmia prevention

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Overview

In ICD patients with potassium ≤4.3 mmol/L, targeting 4.5-5.0 reduced arrhythmia, hospitalization, or death versus standard care.

Clinical takeaway

POTCAST supports actively raising low-normal potassium in selected ICD patients at high risk for ventricular arrhythmias, with kidney function and potassium monitoring.

Key result

Primary events occurred in 22.7% with the potassium-raising strategy vs 29.2% with standard care (HR 0.76; 95% CI 0.61-0.95).

Practice impact

Consider a monitored potassium-raising strategy for ICD patients with plasma potassium ≤4.3 mmol/L.

Evidence

Study design

Multicenter, open-label, event-driven, randomized superiority trial.

Enrollment

1,200

Follow-up

Median 39.6 months (IQR 26.4-49.3).

Geography

Denmark

Clinical question

Does actively increasing plasma potassium to the high-normal range reduce ventricular arrhythmias and related clinical events in ICD patients with potassium levels of 4.3 mmol/L or lower?

Population

  • Adults with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator and baseline plasma potassium ≤4.3 mmol/L.
  • Patients were at high risk for ventricular arrhythmias and had an estimated glomerular filtration rate of at least 30 mL/min/1.73 m².

Intervention

Dietary guidance plus potassium supplementation, a mineralocorticoid receptor antagonist, or both, aiming for plasma potassium of 4.5-5.0 mmol/L, in addition to standard care.

Comparator

Standard care alone.

Primary outcome

Time to first documented sustained ventricular tachycardia or appropriate ICD therapy, unplanned hospitalization longer than 24 hours for arrhythmia or heart failure, or death from any cause.

A treatment strategy aimed at high-normal plasma potassium reduced the risk of the composite primary endpoint compared with standard care.

Hazard ratio / 0.76 / CI 95% CI 0.61-0.95 / p=0.01

Key results

  • Primary endpoint: 22.7% (136/600) with the high-normal potassium strategy vs 29.2% (175/600) with standard care; HR 0.76; 95% CI 0.61-0.95; p=0.01.
  • Event rates were 7.3 vs 9.6 per 100 person-years in the high-normal potassium and standard-care groups, respectively.
  • At 6 months, mean plasma potassium was 4.36 mmol/L in the intervention group vs 4.05 mmol/L in the standard-care group.
  • Hospitalization for hyperkalemia or hypokalemia occurred with similar frequency in both groups.

Harms

  • Hospitalization for hyperkalemia or hypokalemia was uncommon and similar between groups.
  • The strategy requires serial potassium and kidney-function monitoring because potassium supplements and mineralocorticoid receptor antagonists can cause hyperkalemia.

Clinical Use

When to cite

  • When discussing whether low-normal potassium should be actively raised in ICD patients at high risk for ventricular arrhythmias.
  • When considering dietary advice, potassium supplementation, or mineralocorticoid receptor antagonists to reduce appropriate ICD therapy and related clinical events.

Practice impact

  • Provides randomized evidence that low-normal potassium can be a modifiable treatment target in selected patients with ICDs.
  • Supports using dietary guidance, potassium supplementation, and/or mineralocorticoid receptor antagonists as a monitored strategy rather than treating only overt hypokalemia.

Applicability

  • Adults with an ICD or CRT-D, plasma potassium ≤4.3 mmol/L, and eGFR ≥30 mL/min/1.73 m².
  • Most applicable when clinicians can monitor potassium, kidney function, and medication tolerance during titration.

Limitations

  • Open-label trial conducted at three centers in Denmark, which may limit generalizability.
  • The multicomponent intervention cannot isolate the effect of potassium itself from other benefits of mineralocorticoid receptor antagonists.
  • The trial excluded patients with eGFR below 30 mL/min/1.73 m².
  • Fewer than half of intervention participants reached the prespecified potassium target, although the group achieved a meaningful average separation from standard care.

Common misinterpretations

  • Do not extrapolate the result to patients without an ICD or to patients with advanced kidney disease, who were not studied.
  • Do not target 4.5-5.0 mmol/L without monitoring; the intervention was a supervised strategy, not indiscriminate potassium supplementation.
  • The benefit applies to the composite endpoint; the trial was not powered to establish an all-cause mortality benefit by itself.

Related evidence

SCD-HeFT - ContextMADIT-II - ContextRALES - Context

Citation

Jøns C, Zheng C, Winsløw UCG, 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

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.