For patients with cardiovascular disease, efforts to raise potassium levels paid off in terms of a reduction in the risk of ventricular arrhythmias in the POTCAST randomized trial.
High-risk patients, comprising those with implantable cardioverter-defibrillators (ICDs) and either low-to-normal potassium or outright hypokalemia, had improved clinical outcomes over 3 years into the study if they had been randomized to a new potassium target of 4.5-5.0 mmol/L as opposed to usual care, reported Christian Jøns, MD, PhD, of the University of Copenhagen, at the European Society of Cardiology (ESC) Congress.
The study was simultaneously published in the New England Journal of Medicine.
Among patients in the high-normal potassium group, 22.7% experienced a primary composite endpoint event compared with 29.2% of those in the usual-care group (HR 0.76, 95% CI 0.61-0.95), a result driven by arrhythmia-related outcomes of that endpoint:
- Ventricular tachycardia or appropriate ICD therapy: 15.3% vs 20.3% (HR 0.75, 95% CI 0.57-0.98)
- Hospitalization for arrhythmia: 6.7% vs 10.7% (HR 0.63, 95% CI 0.42-0.93)
There were no significant differences in hospitalization for heart failure (3.5% vs 5.5%, respectively; HR 0.64, 95% CI 0.37-1.11), or death from any cause (5.7% vs 6.8%; HR 0.85, 95% CI 0.54-1.34).
Hospitalization for hyperkalemia or hypokalemia was also similar between the two groups.
The link between low (or low-normal) potassium and ventricular arrhythmias is not a new concept.
"For years, we have been teaching to cardiologists in training to target potassium above 4 [mmol/L]," said ESC session panelist Isabelle Van Gelder, MD, PhD, of University Medical Centre Groningen in the Netherlands. "It was known long before but not many do it."
Too much potassium, however, is known to pose a risk to some groups (e.g., people with severely reduced kidney function). What the POTCAST investigators achieved was a "good sweet spot," said fellow panelist Theresa McDonagh, MD, of King's College London. "It's important to hear this message to let potassium go as high as possible without going into the toxic range."
Jøns and colleagues reported that they increased plasma potassium levels from 4.01 mmol/L to 4.36 mmol/L in the intervention arm of POTCAST compared with an increase to 4.05 mmol/L in the usual-care group.
To get there, the patients had been started on mineralocorticoid receptor antagonists and/or potassium supplements with dietary guidance, with existing use of potassium-losing diuretics reduced or stopped; the uptitration period lasted 85 days.
During a press conference, trial co-investigator Henning Bundgaard, MD, also of the University of Copenhagen, noted the general rule of thumb is that the more that food is processed, the more sodium and less potassium it contains.
Included in the dietary guidance provided to study participants was a list of potassium-rich foods such as white beans, beetroot, and cabbage. "We did not recommend [potassium-rich] meat because it is also rich in sodium, which counteracts the increase in plasma potassium," Jøns said.
Notably, the impact of diet alone on potassium levels could not be elucidated from the trial -- the investigators did not track what patients actually ate.
POTCAST was a randomized open-label trial conducted at three clinics in Denmark. The researchers included 1,200 ICD recipients with a baseline plasma potassium level of ≤4.3 mmol/L, who were randomized to the potassium treatment group or to usual care alone. The investigators were not involved with treatment beyond the titration period.
At baseline, the cohort had a mean age of 62.7, and 19.8% were women. ICDs had been placed for primary prevention in 43.3% of the group. Most participants (64.6%) had a history of heart failure, half had a history of ischemic heart disease, and half had cardiomyopathies or primary arrhythmia disorders.
Clinical events were analyzed after a median 39.6 months of follow-up.
Disclosures
The trial was funded by grants from the Independent Research Fund Denmark, the Danish Heart Foundation, and the Novo Nordisk Foundation.
Jøns disclosed being on an endpoint review committee for Biotronik.
Bundgaard reported relationships with Amgen, Bristol Myers Squibb, MSD Denmark, Novo Nordisk, Sanofi, and Genzyme.
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