Clinical Question

Does the use of a partial salt substitute improve health outcomes in older adults at risk of stroke?

Bottom Line

For older adults who have a history or are at risk of stroke, the use of a salt substitute safely reduces their risk of death or stroke. (Level of Evidence = 1b–)

Synopsis

Although salt substitutes have been shown to reduce blood pressure, their effect on patient-oriented outcomes is not known. In this cluster-randomized trial from China, approximately 600 rural villages were randomized to the use of a salt substitute (75% sodium chloride, 25% potassium chloride) or regular salt (100% sodium chloride). The authors recruited approximately 35 people in each village who had a history of stroke or were 60 years or older with hypertension (N = 20,995). Participants were excluded if they or anyone in the household had a contraindication to potassium chloride, such as kidney disease, use of a potassium-sparing drug, or use of potassium supplements. The mean age of participants was 65 years, one-half were women, and 73% had a history of stroke. The groups were balanced at baseline and analysis was by intention to treat. Patients were followed up at six-month intervals for five years (follow-up was delayed for some participants because of the pandemic, but the participants continued to use their assigned compound during that time). Follow-up was 100% for vital status and more than 99% for cardiovascular events. At five years, blood pressure was reduced in the salt substitute group by a mean of 3 mm Hg/1 mm Hg. The risk of stroke was significantly decreased in the salt substitute group (29.1 vs. 33.7 per 1,000 person-years; number needed to treat [NNT] = 217 per year), as was the risk of fatal stroke (6.8 vs. 8.8 per 1,000 person-years; NNT = 500 per year). All-cause mortality was also significantly reduced in the salt substitute group (39.3 vs. 44.6 per 1,000 person-years; NNT = 189 per year). The effect was consistent across subgroups by age, sex, and comorbidities. There was no difference in the likelihood of hyperkalemia between groups.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Population-based

Reference: Neal B, Wu Y, Feng X, et al. Effect of salt substitution on cardiovascular events and death. N Engl J Med. 2021;385(12):1067–1077.

Editor’s Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.