Increasing plasma potassium levels to the high-normal range can improve outcomes in patients with cardiovascular disease (CVD) at high risk of ventricular arrhythmias, a randomised trial has found.
Researchers at Rigshospitalet (Copenhagen University Hospital) in Copenhagen, Denmark, exclusively presented their research at ESC Congress, and simultaneously published their findings in the New England Journal of Medicine.
Hypokalaemia and even low-normal plasma potassium levels can lead to ventricular arrythmias in patients with CVD. This can increase the risk of heart failure and potential death if no intervention is taken, the trial authors noted.
Their POTCAST trial aimed to determine whether increasing potassium levels to the mid-to-high normal range could improve outcomes in patients at high risk of ventricular arrhythmias who had been fitted with an implantable cardioverter defibrillator (ICD) and assess the benefits and risks of this approach.
‘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,’ explained first author Dr Christian Jons, a medical doctor and electrophysiologist at Rigshospitalet.
Potassium and arrhythmia risk
The open-label, randomised controlled POTCAST trial was conducted at three hospital sites in Denmark between March 2019 and September 2024. Trial participants had an ICD or a cardiac resynchronisation therapy defibrillator fitted, and a baseline plasma potassium level of <4.3mmol/l.
A total of 1,200 participants were enrolled consecutively across the sites and were randomly assigned in a 1:1 ratio to a treatment regimen to increase their plasma potassium level to 4.5-5mmol/l.
Methods used included potassium supplementation and/or mineralocorticoid receptor antagonist (MRA) therapy plus dietary guidance and standard care (high-normal potassium group) or standard care only (control group).
Those in the high-normal potassium group received written information on following a potassium-rich diet. Trial medication was also provided to supplement potassium. This was either in the form of potassium chloride tablets or an MRA antagonist drug, and some participants were given both to reach the target level.
Maximum daily doses for MRA antagonist trial medications were 100mg for spironolactone and 50mg for eplerenone. The maximum daily dose for potassium chloride was 4.5g. If suitable for participants, doses of thiazides and loop diuretics were also reduced or discontinued during the trial.
Participants received blood tests and blood pressure measurements every other week at one of the three trial sites. This helped to evaluate whether increases were needed for potassium supplement medications and enabled ongoing assessment of adherence and potential side effects.
After adjustment of treatment, participants had follow-up visits every six months.
The primary endpoint was a composite of documented sustained ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD therapy, unplanned hospitalisation for arrhythmia or heart failure for more than 24 hours, or death from any cause, assessed in a time-to-first-event analysis.
Reduced arrhythmia burden
From mean baseline levels of 4.01mmol/l, plasma potassium levels increased to a mean of 4.36mmol/l in the high-normal potassium group compared with 4.05mmol/l in the control group after six months.
A total of 249 participants reached the target range of optimal plasma potassium levels (4.5-5mmol/l). The primary endpoint was significantly lower in the high-normal potassium group (22.7%) that in the control group (29.2%; hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.61 to 0.95; p=0.015), the study found.
The most common reasons for not reaching the target range were due to participants receiving the maximum tolerated dose (n=146), declining to take more medications (n=71), or due to reaching the maximum daily dose of the trial drugs that were allowed (n=52).
The POTCAST trial identified a ‘treatment-induced increase in plasma potassium level of approximately 0.3mmol/l significantly reduced the arrhythmia burden without increasing the combined risk of hyperkalaemia or hypokalaemia,’ explained lead study author, Professor Henning Bundgaard.
‘The benefits occurred across cardiovascular disease types and regardless of the method used to increase potassium levels, for example, supplementation or MRAs,’ he added.
When it came to safety, hospitalisation due to hyperkalaemia or hypokalaemia occurred in 1% of participants in both groups. An unplanned hospitalisation lasting more than 24 hours and death from all causes occurred in 29.5% of participants in the high-normal potassium group and 33.2% in the control group (HR 0.88; 95% CI 0.72 to 1.08).
Potassium ‘inexpensive and widely available’
Several landmark heart failure trials have seen improvements in cardiovascular outcomes with the use of MRAs as this has been accompanied by increases in potassium levels, Professor Bundgaard explained.
‘The findings of the POTCAST trial have led us to speculate that increased potassium levels may, at least partially, be responsible for MRAs’ positive outcomes, rather than merely being a side effect,’ he added.
‘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 article was originally published by our sister publication Hospital Healthcare Europe.
