Restricting sodium intake often is recommended for patients with HF, based on basic and clinical models that have pointed to a role for sodium and fluid handling in the pathophysiology of the condition. However, the clinical evidence underlying this practice is inconsistent, and as a result, clinicians treating patients with HF are faced with varying recommendations about dietary sodium intake in guidelines from major organizations (Table). A systematic review and meta-analysis of randomized controlled trials (RCTs) suggests that sodium restriction is not associated with fewer deaths or hospitalizations in patients with HF. It may, however, be associated with improvements in symptoms and QOL, according to the report published in Circulation: Heart Failure.
“This is a complicated area with only a few, small clinical trials until recently. We published results of the larger SODIUM-HF trial in 2022,” says Justin A. Ezekowitz, MBBCh, MSc. “This analysis brings together data from SODIUM-HF with the smaller trials in an update that has changed our viewpoint on the field.”
Representing the Clinical Area Well
“We primarily looked at clinical outcomes, recognizing that there were key differences in the design of the trials, including the patients, the lengths of the studies, and the eras in which they were completed,” says Dr. Ezekowitz. “We used standard techniques for systematic review and meta-analysis endorsed by several large international organizations.”
For the study, the researchers searched Cochrane Central, MEDLINE, Embase Ovid, and CINAHL through April 2, 2022. RCTs were included if they investigated the effects of sodium/salt restriction as compared to no restriction on clinical outcomes in patients with HF. Outcomes of interests were mortality, hospitalization, change in New York Heart Association (NYHA) functional class, and QOL.
Says Dr. Ezekowitz, “We incorporated 17 RCTs, which represent 1,683 patients, including one trial that had not been identified by previous investigators. Thus, we believe the nature of our analysis represents the clinical area well.”
Implications for Clinical Practice
“Overall, we identified that there is no additional reduction in hospitalizations or risk for death with dietary interventions that lower dietary sodium intake,” says Dr. Ezekowitz. “Importantly, we also found that there is no additional harm, which is another key message for our patients and clinicians if they are going to follow a lower sodium diet.”
Odds ratios (ORs) for all-cause death and hospitalization were 0.95 and 0.84, respectively, and for the composite of death/hospitalization, the OR was 0.88. The results were similar in different subgroups, except for a numerically lower risk of death with reduced sodium intake reported in RCTs with dietary sodium in the 2,000-3,000 mg/d range compared with less than 2,000 mg/d (and in RCTs with versus without fluid restriction as a co-intervention). Subgroups included HF class (with preserved vs reduced ejection fraction), setting (outpatient vs inpatient) and follow-up periods (<6 or ≥6 months).
Eight studies reported a change in NYHA class with salt restriction. Of them, five showed no difference between arms in terms of change in NYHA class from baseline to follow-up. However, two of the three remaining studies—which represented the majority of patients in the pooled cohort—did suggest an improvement in NYHA class with sodium restriction.
In terms of QOL, six RCTs showed improvement or trends for improvement with salt restriction, while three trials showed no benefit of salt restriction on QOL. One study suggested a trend for improvement in the Minnesota Living With Heart Failure Questionnaire in the control group, but not in the intervention group.
According to the authors, their study has several limitations. Not all outcomes were reported in all of the trials included in the meta-analysis. Most studies enrolled fewer than 100 participants, meaning that SODIUM-HF made a high contribution to the results of the pooled analysis. The lack of effect of sodium dietary restriction on clinical outcomes also cannot be ascribed to any specific amount of sodium, because the levels of restriction varied across trials.
“There still remains a great deal of uncertainty as to whether or not alterations in either diet or fluid intake can change any clinical outcomes in HF,” says Dr. Ezekowitz. “But recent trials have shown that sodium restriction does not appear to be effective in reducing risk of hospitalization or death. We need to understand if there are certain groups for whom it could be beneficial or potentially harmful. HF patients often ask about whether they should change their diet, so it is important to provide robust clinical trial information to try to inform that decision.”