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Randomized Controlled Trial
. 2025 Apr 1;10(4):343-350.
doi: 10.1001/jamacardio.2024.5417.

Salt Substitution and Recurrent Stroke and Death: A Randomized Clinical Trial

Xiong Ding  1   2 , Xinyi Zhang  3 , Liping Huang  4 , Shangzhi Xiong  4 , Zhifang Li  5 , Yi Zhao  6 , Bo Zhou  7 , Xuejun Yin  4 , Bingqing Xu  8 , Yanfeng Wu  9 , Bruce Neal  4   10 , Maoyi Tian  3   4   11 , Lijing L Yan  1   2
Affiliations
Randomized Controlled Trial

Salt Substitution and Recurrent Stroke and Death: A Randomized Clinical Trial

Xiong Ding et al. JAMA Cardiol. .

Abstract

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.

Trial registration: ClinicalTrials.gov Identifier: NCT02092090.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Huang, Wu, and Neal reported receiving grants from the National Health and Medical Research Council of Australia during the conduct of the study. No other disclosures were reported.

Comment on

References

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