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Data from SODIUM-HF indicates reduction of dietary sodium intake was not associated with a statistically significant reduction of a composite of all-cause death, cardiovascular-related hospitalizations, and cardiovascular-related emergency department visits.
Much to the chagrin of many in the field, the largest and longest randomized clinical trial to study dietary sodium reduction for heart failure has returned mixed results.
Presented at the American College of Cardiology’s 71st Annual Scientific Sessions less than a year after the landmark Salt Substitute and Stroke Study (SSaSS) made headlines at ESC 2021, the SODIUM-HF trial failed to meet its primary endpoint, which was reduction of a composite of all-cause death and cardiovascular-related hospitalizations, but did find reduction of dietary sodium was associated with improvements in quality of life and NYHA class for patients with heart failure.
“While the intervention didn’t reduce clinical events, we found the low-sodium group had modest improvements in quality of life and New York Heart Association heart failure class, which we think will be quite important and valued by patients and clinicians alike,” said Justin A. Ezekowitz, MBBCh, professor of medicine at the University of Alberta, Edmonton in Canada, and the study’s lead author. “We need to explore further whether there might be a way to individualize recommendations from our trial to see if the quality-of-life benefits might make it worth it for certain patients [to reduce sodium intake].”
Although discussion around the impact of sodium intake on cardiovascular health have persisted for decades, until recently there has been few trials examining the effect of reducing dietary sodium intake on cardiovascular events. In SSaSS, use of a salt substitute was associated with a 14% reduction in risk of stroke and 13% reduction in risk of cardiovascular events, but SODIUM-HF did not experience the same success in terms of meeting its primary endpoint.
An international, open-label, randomized, controlled trial that enrolled patients at 26 sites in Australia, Canada, Chile, Colombia, Mexico, and New Zealand, the trial enrolled patients aged 18 years and older with NYHA class 2-3 heart failure already receiving optimally tolerated guideline-directed medical therapy and randomized them in a 1:1 ratio to usual care or a low sodium diet of less than 1500 mg of sodium per day. The trial’s primary outcome was a composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months.
Secondary outcome measures included time to first event within the event type within 12 months and 24 months, quality of life as measured via the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, clinical summary score, and physical limitation score, change in 6-minute walk distance; and change in NYHA functional class. Safety was also assessed as part of study protocol but no specific criteria for adverse events was used and safety was assessed by site personnel.
From March 24, 2014 through December 9, 2020, 806 patients were enrolled and underwent randomization in the study. Of these, 397 were randomized to a low sodium diet and 409 were randomized to usual care. The overall cohort had a median age of 67 (IQR, 58-74) years, 33% were women, the median ejection fraction was 36% (IQR, 27-49), and 33% had been admitted to the hospital for heart failure in past 12 months.
From baseline to 12 months, the median daily sodium intake decreased from 2286 mg (IQR, 1653-3005) to 1658 mg (IQR, 1301-2189) among those in the low sodium group. During the same time, daily median sodium intake decreased from 2119 mg (IQR, 1673-2804) to 2073 mg (IQR, 1541-2900) among those in the usual care group.
The investigators’ primary analysis of 12-month data indicated a primary outcome event had occurred among 15% in the low sodium drop and 17% in the usual care group (HR, 0.89 [95% CI, 0.63-1.26]; P=.53). When assessing individual components of the primary endpoint, investigators found all-cause death had occurred among 6% of patients in the low sodium group and 4% of patients in the usual care group (HR, 1.38 [95% CI, 0.73-2.60]; P=.32), cardiovascular-related hospitalizations occurred in 10% in the low sodium group and 12% in the usual care group (HR, 0.82 [95% CI, 0.54-1.24]; P=.36), and cardiovascular-related emergency department visits occurred in 4% in the low sodium group and 4% in the usual care group (HR, 1.21 [905% CI, 0.60-2.41]; P=.60).
“All three scores were significantly better in the low-sodium group compared to the usual care group, and these improvements in quality-of-life scores were consistent across all the assessments and across time,” said Ezekowitz, who is also director of cardiovascular research at the University of Alberta and codirector of the Canadian VIGOUR Center. “This improvement was quite marked compared to other clinical trials, for example, trials for pharmacological interventions.”
This study, “Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial,” was presented at ACC.22 and simultaneously published in The Lancet.