Salt Substitution and Recurrent #Stroke and DeathA Randomized Clinical Trial

Question  Does the use of a reduced-sodium, added-potassium salt substitute vs regular salt decrease the risk of stroke recurrence and death in patients with a history of stroke?

Findings  In this prespecified subgroup analysis of the Salt Substitute and Stroke Study (SSaSS) trial involving 15 249 patients with stroke, the use of a salt substitute led to a 14% reduction in the risk of recurrent stroke and a 12% reduction in mortality.

Meaning  Results suggest that salt substitution significantly reduced the risks of stroke recurrence and death and is a novel and practical therapeutic option for patients with stroke.

Importance  The direct effect of consumption of salt substitutes on recurrent stroke and mortality among patients with stroke remains unclear.

Objective  To evaluate the effects of salt substitutes vs regular salt on the incidence of recurrent stroke and mortality among patients with stroke.

Design, Setting, and Participants  The Salt Substitute and Stroke Study (SSaSS), an open-label, cluster randomized clinical trial, was conducted in 600 northern Chinese villages (clusters). Patients who self-reported a hospital diagnosis of stroke were included in this prespecified subgroup analysis. Data were analyzed from November 2023 to August 2024.

Interventions  Participants were assigned to use either a salt substitute, consisting of 75% sodium chloride and 25% potassium chloride by mass, or regular salt.

Main Outcomes and Measures  The primary outcome was recurrent stroke.

Results  After excluding 5746 persons without a baseline history of stroke, 15 249 patients with stroke (mean [SD] age, 64.1 [8.8] years; 6999 [45.9%] female; 8250 male [54.1%]) were included. Over a median (IQR) follow-up of 61.2 (60.9-61.6) months, the mean difference in systolic blood pressure was −2.05 mm Hg (95% CI, −3.03 to −1.08 mm Hg). A total of 2735 recurrent stroke events (691 fatal and 2044 nonfatal) and 3242 deaths were recorded. Recurrent stroke was significantly lower in the salt substitute vs regular salt group (rate ratio [RR], 0.86; 95% CI, 0.77-0.95; P = .005), with larger effects on hemorrhagic stroke (relative reduction, 30%; P = .002). Death rates were also significantly lower (RR, 0.88; 95% CI, 0.82-0.96; P = .003), with larger effects on stroke-related deaths (relative reduction 21%; P = .01). No significant difference was observed for hyperkalemia (RR, 1.01; 95% CI, 0.74-1.38; P = .96).

Conclusions and Relevance  Results of this cluster trial demonstrate that salt substitution was safe, along with reduced risks of stroke recurrence and death, which underscores large health gains from scaling up this low-cost intervention among patients with stroke.

https://jamanetwork.com/journals/jamacardiology/article-abstract/2829790