Patients with advanced heart failure, who are already followed closely, might be a good population to focus on, one expert says.
MADRID, Spain—Increasing low potassium levels improves clinical outcomes among patients with cardiovascular disease and a high risk for ventricular arrhythmias, the randomized POTCAST trial shows.
Those who had their potassium boosted versus those who didn’t had a 24% lower relative risk of a composite outcome of appropriate implantable cardioverter-defibrillator (ICD) therapy, sustained ventricular arrhythmia, unplanned hospitalization for arrhythmia or heart failure, or all-cause mortality.
Christian Jøns, MD, PhD (Rigshospitalet – Copenhagen University Hospital, Denmark), reported the results here at the European Society of Cardiology Congress 2025.
The improvement in outcomes was both statistically and clinically significant, senior investigator Henning Bundgaard, MD, DMSc (Rigshospitalet – Copenhagen University Hospital), said at a press conference. This benefit was accomplished with “old and simple drugs” that are well-known to clinicians, he said, alluding to the use of mineralocorticoid receptor antagonists (MRAs).
“They are safe, they are well tolerated by most patients, and they are cheap,” he added, saying that “this could certainly become a widely cost-effective regimen in cardiology.”
There was no increase in hospitalizations for hyper- or hypokalemia compared with standard care, although Bundegaard cautioned against using such a strategy in patients with severely reduced kidney function.
The findings were published simultaneously online in the New England Journal of Medicine.
The POTCAST Trial
Humans evolved eating a diet rich in potassium and low in sodium, but modern Western diets replete with processed foods typically contain more sodium and less potassium, which is important for cardiac function, Bundgaard told the media. Observational studies have demonstrated a link between low levels of the electrolyte and greater risks of arrhythmias, heart failure, and death. Even within the normal range of 3.5 to 5.0 mmol/L, lower levels equate to poorer clinical outcomes compared with higher levels.
POTCAST, an open-label trial conducted at three sites in Denmark, was designed to test the idea that uptitrating potassium levels through various means could improve outcomes in vulnerable patients. Investigators enrolled 1,200 patients (mean age 62.7 years; 19.8% women) deemed to have a high risk for ventricular arrhythmias, defined as having either an ICD or cardiac resynchronization therapy defibrillator, and a baseline plasma potassium level ≤ 4.3 mmol/L.
Most patients (64.6%) had a history of heart failure. Half had a history of ischemic heart disease, whereas the other half had cardiomyopathies or primary arrhythmia disorders.
Patients were randomized to potassium uptitration plus standard care or standard care alone. In the intervention group, potassium levels were increased to a target of 4.5 to 5.0 mmol/L using potassium supplementation and/or MRAs along with dietary guidance and, when possible, decreased use of thiazide and loop diuretics.
At baseline, the mean potassium level was 4.01 mmol/L in both groups. This increased to 4.36 mmol/L in the intervention group after a median adjustment period of 85 days and to 4.05 mmol/L in the control group after 6 months.
The primary endpoint encompassed documented sustained ventricular tachycardia with a rate > 125 bpm lasting more than 30 seconds, appropriate ICD therapy (either shocks or antitachycardia pacing), unplanned hospitalizations for arrhythmia or heart failure lasting more than 24 hours and resulting in a change in drug or invasive treatment, or all-cause death.
Through a median follow-up of 39.6 months, patients who had their potassium boosted had a lower rate of the composite endpoint (22.7% vs 29.2%; HR 0.76; 95% CI 0.61-0.95). The effects were consistent across various subgroups, including patients who were or were not taking MRAs at the end of the adjustment period and those who did or did not reach the plasma potassium target.
The difference between groups was driven by reductions in appropriate ICD therapy (15.3% vs 20.3%; HR 0.75; 95% CI 0.57-0.98) and unplanned hospitalizations for cardiac arrhythmias (6.7% vs 10.7%; HR 0.63; 95% CI 0.42-0.93). There were no significant effects on unplanned hospitalizations for heart failure (3.5% vs 5.5%; HR 0.64; 95% CI 0.37-1.11) or all-cause death (5.7% vs 6.8%; HR 0.85; 95% CI 0.54-1.34).
In terms of safety, there was no significant difference in the number of hospitalizations for hyperkalemia, hypokalemia, or kidney failure between the intervention and control arms (17 vs 12; HR 1.75; 95% CI 0.80-3.82).
‘An Easy Win’
Bundegaard noted that the findings of POTCAST confirm the positive effects of high potassium that have been seen in many observational studies and clinical trials of MRAs in heart failure, in which the increase in plasma potassium was often described as an adverse effect. But it could be, the researchers say, that the increases in potassium explain some of the beneficial effects of these drugs.
“With a broader view, we can say that higher dietary intake of potassium may not only benefit patients with heart diseases, but probably all of us, so maybe we should all reduce sodium and increase potassium content in our food,” Bundgaard said.
I love this kind of study looking for simple everyday solutions to some of our more challenging clinical problems. Peter Weiss
Commenting for TCTMD, Peter Weiss, MD (Banner – University Medical Center Phoenix, AZ), said that, “in general, I love this kind of study looking for simple everyday solutions to some of our more challenging clinical problems. This sort of thing doesn’t require fancy drugs and doesn’t require fancy procedures or expensive devices.” He added that POTCAST was well done, with a relatively high number of participants.
Weiss cautioned, however, against rolling out the potassium uptitration strategy tested in POTCAST without the proper support system in place.
“For the broader audience, especially in the United States, we need to keep in mind the potential limitations of replicating this level of care that they’re capable of doing in that part of the world, where you’ve got a more organized healthcare system,” he said. “We want to make sure, of course, if you’re going to do this kind of thing, that the patient’s medications are given appropriately, that the supplements are given appropriately, that there’s good compliance, that we have appropriate laboratory follow-up to make sure that they’re staying within the target range, etc.”
Employing this approach more broadly without that attention might limit the observed benefits and raise the risk of hyperkalemia, he said.
The obvious group in which to try potassium uptitration is patients with advanced heart failure, who are already being followed closely and who are likely to be taking MRAs already, Weiss suggested.
“I do think this is scalable, and I think it’s an easy win as long as the physicians and the patients are able to work closely enough together to have good patient compliance and the adequate close follow-up to assure that they’re staying within the target range,” he said.