A low-sodium diet was not associated with a reduction in future clinical events in a new study in outpatients with heart failure. But there was a moderate benefit on quality of life and New York Heart Association (NYHA) functional class.
Results from the SODIUM-HF trial were presented today at the American College of Cardiology (ACC) Scientific Session 2022, conducted virtually and in person in Washington, DC. They were also simultaneously published online in The Lancet.
The study found that a strategy to reduce dietary sodium intake to less than 1500 mg per day was no more effective than usual care in reducing the primary endpoint for risk of hospitalization or cardiovascular emergency department visits or all-cause death at 12 months.
“This is the largest and longest-running trial to examine the issue of dietary sodium reduction in patients with heart failure,” said lead author Justin Ezekowitz, MBBCh, of the Canadian VIGOR Center at the University of Alberta, Edmonton, Canada. theheart.org | Medscape Cardiology.
But he pointed out that there were fewer events than expected in the study, which was stopped early due to a combination of futility and practical difficulties caused by the COVID pandemic, so it would have may have been undernourished. Ezekowitz also suggested that greater sodium reduction than achieved in this study or longer follow-up might be needed to show an effect on clinical events.
“We hope that others will do additional studies on sodium as well as other dietary recommendations as part of a complete diet for patients with heart failure,” he commented.
Ezekowitz said the study results don’t allow for general recommendations on reducing sodium intake in heart failure.
But he added: “I don’t think we should reverse sodium reduction in this population. I think we can tell patients that reducing dietary sodium can potentially improve symptoms and quality of life, and I will continue Recommend reducing sodium as part of an overall healthy diet We don’t want to throw the baby out with the bathwater.
Ezekowitz noted that heart failure is associated with neurohormonal activation and autonomic control abnormalities that lead to sodium and water retention; thus, dietary sodium restriction has historically been recognized as a mechanism to prevent fluid overload and subsequent clinical outcomes; however, clinical trials so far have shown mixed results.
“Guidelines strongly recommended a reduction in sodium intake in patients with heart failure, but this advice has receded in recent years due to lack of data. Most heart failure guidelines do not now no recommendations on dietary sodium,” he said. .
SODIUM-HF was a pragmatic, multinational, open-label, randomized trial conducted in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand), which included 809 patients (median age, 67 years) with chronic heart failure (NYHA Functional Class II–III) who were receiving medical treatment consistent with guidelines and optimally tolerated. They were randomly assigned to usual care according to local guidelines or to a low sodium diet below 100 mmol (<1500 mg/day). Patients whose initial sodium intake was less than 1500 mg/day were excluded.
In the intervention group, patients were asked to follow low-sodium menus developed by dietitians located in each region. They also received behavioral counseling from trained dieticians, doctors or nurses.
Dietary sodium intake was assessed using a 3-day food diary (including 1 weekend day) at baseline, at 6 months and at 12 months in both groups and, for the group d. intervention, also at 3 and 9 months to monitor and support food adherence.
Ezekowitz explained that while the best method for measuring sodium levels is normally a 24-hour urine sodium, that would be impractical in a large clinical trial. Additionally, he pointed out that urinary sodium is not an accurate measure of actual sodium levels in patients taking diuretics, so it is not a good measure to use in a population with heart failure.
“The food logging method for assessing sodium levels has been well validated; I think we measured it as accurately as we could have,” he added.
Results showed that between baseline and 12 months, median sodium intake increased from 2286 mg/day to 1658 mg/day in the low sodium group and from 2119 mg/day to 2 073 mg/day in the usual care group. The median difference between the groups was 415 mg/day at 12 months.
At 12 months, primary outcome events (cardiovascular hospitalization or emergency room visits or death from any cause) occurred in 15% of patients in the low sodium diet group and 17% in the usual care group ( Dangerousness rate [HR]0.89 [95% CI, 0.63 – 1.26]; P = 0.53).
Death from any cause occurred in 6% of patients in the low sodium diet group and 4% of those in the usual care group (HR, 1.38; P = 0.32). Cardiovascular disease-related hospitalization occurred in 10% of the low sodium group and 12% of the usual care group (HR, 0.82; P = 0.36), and CVD-related ED visits occurred in 4% of both groups (HR, 1.21; P = .60).
The lack of treatment effect for the primary outcome was consistent across most prespecified subgroups, including those with higher or lower baseline sodium intake. But there was a suggestion of a greater reduction in the primary outcome in people younger than 65 than in those 65 and older.
Quality of life measures on the Kansas City Cardiomyopathy Questionnaire (KCCQ) suggested a benefit in the low sodium group, with mean differences between the groups in change from baseline to 12 months of 3, 38 points in the overall summary score, 3.29 points in the summary clinical score and 3.77 points in the physical limitation score (all differences were statistically significant).
There was no significant difference in 6-minute walking distance at 12 months between the low sodium diet group and the usual care group.
NYHA functional class at 12 months differed significantly between the groups; the low-sodium diet group had a greater likelihood of improving one NYHA class than the usual care group (odds ratio, 0.59; P = 0.0061).
No safety events related to study treatment were reported in either group.
Ezekowitz said that to determine if longer follow-up can show a difference in events, further analyzes are planned at 2 years and 5 years.
Questions about food recall and blindness
Commenting on the results of the latest clinical trial session at the ACC meeting, Biykem Bozkurt, MD, professor of medicine at Baylor College of Medicine, Houston, Texas, praised Ezekowitz for conducting this trial.
“We have been searching for the holy grail of sodium reduction in heart failure for a very long time, so I must commend you and your team for taking on this challenge, especially during the pandemic,” she said. .
But Bozkurt questioned whether the intervention group actually had a significant reduction in sodium given that this was measured by food recall and may have been explained by under-reporting of certain dietary intakes.
Ezekowitz replied that the patients acted as their own controls in that caloric intake, fluid intake and weight were also assessed and did not change. “So I think we’ve had a significant reduction in sodium,” he said.
Bozkurt also asked if the improvements in quality of life and functional status were reliable given that this was an open-label study.
At this point, Ezekowitz pointed out that the KCCQ quality of life measure was a highly validated instrument and that improvements were seen in these measures at 3, 6 and 12 months. “It’s not like these are false findings, so I think we have to take this as a real result,” he argued.
Commenting on the study at an ACC press conference, Mary Norine Walsh, MD, director of heart failure and heart transplant programs at St. Vincent Heart Center in Indianapolis, Indiana, said the trial had answered two important questions: reducing sodium in heart failure may not reduce heart failure hospitalizations/deaths, but that patients feel better.
“I think we can safely tell patients that if they slip a bit, they might not end up in the hospital,” she added.
This study was funded by the Canadian Institutes of Health Research and the University Hospital Foundation (Edmonton, Alberta, Canada) and the Health Research Council of New Zealand. Ezekowitz reports research grants from American Regent, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, eko.ai, US2.ai, Merck, Novartis, Otsuka, Sanofi, and Servier and consultancy fees from American Regent , Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Merck, Novartis, Otsuka, Sanofi and Servier.
American College of Cardiology (ACC) 2022 Scientific Session. Presented April 2, 2022.
Lancet. Published online April 2, 2022. Summary
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