May 15, 2026European Heart Journal
Increasing plasma potassium and risk of atrial fibrillation: the POTCAST trial
Key result
Potassium-increasing treatment cuts AF-related events ~35% vs standard care in ICD or CRT-D patients.
- HR 0.65
- 95% CI 0.45-0.93
- P=0.02
- n=1,200
Why the study?
Hypokalaemia and low-normal plasma potassium are associated with increased atrial fibrillation risk, but whether potassium-increasing treatment reduces atrial fibrillation-related clinical events was unknown.
Does potassium-increasing treatment reduce the risk of atrial fibrillation-related clinical events in adults with an ICD or CRT-D and plasma potassium ≤4.3 mmol/L?
Key Points
- To determine whether increasing plasma potassium levels to a high-normal target range reduces the risk of atrial fibrillation-related clinical events in patients with cardiac defibrillators.
- Prespecified analysis of the randomized POTCAST trial involving 1,200 adults (median age 64 years, 80.3% male) with an ICD or CRT-D and plasma potassium ≤4.3 mmol/L.
- Participants were randomized 1:1 to potassium-increasing treatment plus standard care (high-normal potassium group, n=600) or standard care alone (control group, n=600).
- Evaluated a composite endpoint of AF-related acute hospitalizations, inappropriate shocks, electrical cardioversion, catheter ablation, or amiodarone loading over a median follow-up of 3.3 person-years with death as a competing risk.
- Plasma potassium increased by 0.3 mmol/L following uptitration in the high-normal potassium group compared with the control group.
- The primary composite endpoint occurred in 48 participants in the high-normal potassium group (8.0%, 2.80 events per 100 person-years) versus 73 participants in the control group (12.2%, 4.30 events per 100 person-years) (subdistribution HR 0.65; 95% CI, 0.45–0.93; P = 0.02).
- The relative risk reduction was consistent across prespecified subgroups, including patients with and without a prior history of atrial fibrillation.
Study Design
Type
RCT (n=1,200)
Randomization
randomized
Structured PICO
Does potassium-increasing treatment reduce the risk of atrial fibrillation-related clinical events in adults with an ICD or CRT-D and plasma potassium ≤4.3 mmol/L?
P
Population
1,200 adults (median age 64, 19.7% female) with an ICD or CRT-D and plasma potassium ≤4.3 mmol/L, followed for a median of 3.3 person-years.
I
Intervention
Potassium-increasing treatment added to standard care (uptitration to high-normal potassium)
C
Comparator
Standard care alone
O
Outcome
Composite of acute hospitalizations due to atrial fibrillation leading to a change in pharmacological treatment or due to inappropriate shock therapy, hospitalization for electrical cardioversion or ablation of atrial fibrillation, and loading with amiodarone for atrial fibrillationcomposite
Main Result
Hazard Ratio: 0.65 (95% CI 0.45–0.93)
Absolute Event Rate: 8% vs 12.2%
p-value: p=0.02
Uptitration of plasma potassium levels within the normal range significantly reduces the risk of atrial fibrillation-related clinical events in patients with an ICD or CRT-D.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
DCDr. Christian Jons
“There is some evidence from observational studies to suggest that low plasma potassium levels are associated with increased risk of dangerous alterations in heart rhythms and that potassium levels in the upper normal level have protective effects. We conducted the POTCAST trial to assess the benefits and risks of targeting high-normal potassium levels in patients at high risk of ventricular arrhythmias with an ICD.”
“The findings of POTCAST lead us to speculate that increased potassium levels may, at least partially, be responsible for MRAs' positive outcomes, rather than merely being a side effect. We believe the time is right to consider increasing potassium levels to the mid-to-high normal range as an inexpensive and widely available treatment strategy in patients with a broad spectrum of cardiovascular diseases associated with a high risk of ventricular arrhythmia.”
“This benefit was accomplished with “old and simple drugs” that are well-known to clinicians. They are safe, they are well tolerated by most patients, and they are cheap, this could certainly become a widely cost-effective regimen in cardiology.”
Implication
May warrant potassium uptitration in ICD/CRT-D patients with low-normal levels; extends observational data with randomized confirmation.
Abstract
BACKGROUND AND AIMS: Hypokalaemia and low-normal plasma potassium levels are associated with increased risk of atrial fibrillation. This study examined if potassium-increasing treatment reduces the risk of atrial fibrillation-related clinical events. METHODS: This is a prespecified analysis of the POTCAST trial. Adults with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) and plasma potassium ≤4.3 mmol/L were randomized to potassium-increasing treatment and standard care (high-normal potassium group) or standard care alone (control group). The endpoint was a composite of acute hospitalizations due to atrial fibrillation leading to a change in pharmacological treatment or due to inappropriate shock therapy, hospitalization for electrical cardioversion or ablation of atrial fibrillation, and loading with amiodarone for atrial fibrillation. The endpoint was evaluated in time-to-first-event analyses with death as competing risk. RESULTS: Among 1200 participants [600 in each group, median age 64 years (interquartile range, 56-72), 80.3% male], 390 (32.5%) had a history of atrial fibrillation. Plasma potassium increased by .3 mmol/L after uptitration in the high-normal potassium group compared with the controls. After a median follow-up of 3.3 person-years, the endpoint had occurred in 48 participants in the high-normal potassium group (8.0%, 2.80 events per 100 person-years), when compared with 73 participants in the control group (12.2%, 4.30 events per 100 person-years) (subdistribution hazard ratio, .65; 95% confidence interval, .45-.93, P = .02). The treatment effect appeared similar across subgroups, including those with vs without a history of atrial fibrillation. CONCLUSIONS: In adults with any cardiac disease, treated with an ICD or CRT-D, uptitration of plasma potassium levels within the normal range reduced the risk of atrial fibrillation-related clinical events.
Discussion
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Cite This Study
Zheng et al. (2026) conducted an RCT in Atrial fibrillation risk in patients with ICD or CRT-D (n=1,200). Potassium-increasing treatment vs. Standard care alone was evaluated on Composite of acute hospitalizations due to atrial fibrillation leading to a change in pharmacological treatment or due to inappropriate shock therapy, hospitalization for electrical cardioversion or ablation of atrial fibrillation, and loading with amiodarone for atrial fibrillation (HR 0.65, 95% CI 0.45-0.93, p=0.02). Potassium-increasing treatment reduced atrial fibrillation-related clinical events compared to standard care in adults with an ICD or CRT-D (8.0% vs 12.2%; HR 0.65; 95% CI 0.45-0.93; P=0.02).