CLINICAL IMPACT RATINGS
THERAPEUTICS
GM
C
In adults at high risk for ventricular arrhythmia, treatment
to increase potassium to high-normal levels improved a composite outcome
ACP Journal Club Editorial Team at McMaster University
Question: In adults at high risk for ventricular arrhythmia, what are the
efficacy and safety of treatment aiming to increase plasma potassium to
high-normal levels?
Patients: 1200 adults (mean age, 63 y; 80% men; mean plasma potassium level, 4.01 mmol/L) who had an ICD or cardiac resynchronization therapy defibrillator and plasma potassium level ≤4.3 mmol/L. Key exclusion:
estimated glomerular filtration rate <30 mL/min/1.73 m2.
Design: Randomized controlled trial (POTCAST [Targeted Potassium Levels
to Decrease Arrythmia Burden in High-Risk Patients with Cardiovascular
Diseases]).
Interventions: Treatment aiming to increase plasma potassium to a highnormal level (4.5 to 5.0 mmol/L), including use of potassium supplementation and/or mineralocorticoid receptor antagonists and provision of information on a potassium-rich diet, plus standard care (n = 600); or standard
care alone (n = 600).
Blinding: Treatment allocation concealed; blinded (outcome adjudication
committee).*
Setting: 3 centers in Denmark where implantable cardioverter-defibrillators
(ICDs) were implanted.
*See Glossary. Some information provided by authors.
Results: Treatment to increase plasma potassium to high-normal levels + SC vs. SC alone in adults at high risk for ventricular
arrhythmia
Outcomes
Events/100 patient-y
HR (95% CI) at a
median 40 mo
Treatment to increase plasma
potassium level + SC
SC alone
Composite primary outcome†
7.30
9.60
0.76 (0.61 to 0.95)‡
Hospitalization for hypokalemia, hyperkalemia, or kidney failure
0.93
0.55
1.75 (0.80 to 3.82)
Mean plasma potassium levels increased from 4.01 mmol/L at baseline to 4.36 mmol/L after 85 d in the group that received treatment to increase
plasma potassium level and to 4.05 mmol/L after 6 mo in the SC-alone group.
HR = hazard ratio; ICD = implantable cardioverter-defibrillator; SC = standard care; CI defined in Glossary. Primary outcome indicated by boldface.
†Sustained ventricular tachycardia (>125 beats/min lasting >30 s) or appropriate ICD therapy, documented by electrocardiography or ICD cardiac electrogram (5.05 vs.
6.69 events/100 patient-y); unplanned hospitalization lasting >24 h for arrhythmia (2.19 vs. 3.51 events/100 patient-y) or heart failure (1.15 vs. 1.81 events/100
patient-y) that led to a change in treatment; or all-cause mortality (1.86 vs. 2.25 events/100 patient-y).
‡NNT = 13 (CI, 2 to 14).
Bottom line:
In adults at high risk
for ventricular
arrhythmia, adding
treatment aimed at
increasing plasma
potassium to highnormal levels to
standard care improved
a composite clinical
outcome at a median
40 months.
Source Citation: Jøns C, Zheng C, Winsløw UC, et al; POTCAST Study Group. Increasing the potassium level in patients at high risk for ventricular arrhythmias. N Engl J Med. 2025;393:1979-1989.
Commentary:
Mohammed Ruzieh, MD, MSCE
Northwestern University
Chicago, Illinois, USA
The POTCAST trial by Jøns and colleagues sought to answer an important
question: In patients with ICDs, should we target plasma potassium to
high-normal levels (4.5 to 5.0 mmol/L)? We know that potassium levels
exhibit a U-shaped relationship with mortality, meaning that both low and
high potassium levels are associated with increased risk for death (1).
POTCAST found that treatment aiming to increase plasma potassium to
high-normal levels in this population improved a composite clinical outcome that included ventricular arrhythmias, hospitalization, or death.
There are important issues to consider before applying the trial results to
patients in everyday practice. First, the trial was open-label, which potentially introduced biases, such as performance bias (2), which may have
influenced the results. Second, the trial enrolled only patients with an ICD.
Patients have a defibrillator for a reason—high risk for or previous significant ventricular tachycardia or fibrillation. Consequently, their hearts may
This article was published at Annals.org on 6 January 2026.
doi:10.7326/ANNALS-25-04843-JC
be more susceptible to fluctuations in plasma potassium levels (3).
Therefore, the findings of POTCAST may not be generalizable to broader
patient populations. Finally, the observed benefit could be secondary to
prevention of low potassium levels (hypokalemia) rather than the effect of
maintaining high-normal levels. Nevertheless, the study findings support
treatment aiming to increase plasma potassium to high-normal levels in
patients with ICDs.
Disclosures: Disclosure form is available with the article online.
References
1.
2.
3.
Jønsson SS, Sørensen SA, Krøgh ST, et al. Short-term prognosis of changes in plasma
potassium following an episode of hyperkalaemia in patients with chronic heart failure. Eur J
Intern Med. 2023;118:82-88.
Mansournia MA, Higgins JP, Sterne JA, et al. Biases in randomized trials: a conversation
between trialists and epidemiologists. Epidemiology. 2017;28:54-59.
Ferreira JP, Butler J, Rossignol P, et al. Abnormalities of potassium in heart failure: JACC
State-of-the-Art review. J Am Coll Cardiol. 2020;75:2836-2850.
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