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

Summary

In a prespecified subgroup of 15,249 stroke survivors within the SSaSS cluster RCT, a 75% NaCl/25% KCl salt substitute reduced recurrent stroke (RR 0.86) and all-cause mortality (RR 0.88) over a median 61.2 months, with a −2.05 mm Hg systolic BP difference and no excess hyperkalemia. Benefits were larger for hemorrhagic stroke and stroke-related deaths.

Key Findings

• Recurrent stroke reduced with salt substitute vs regular salt (RR 0.86; 95% CI 0.77–0.95; P=.005).
• All-cause mortality reduced (RR 0.88; 95% CI 0.82–0.96; P=.003), with larger effects on stroke-related deaths.
• No increase in hyperkalemia (RR 1.01; 95% CI 0.74–1.38; P=.96); systolic BP decreased by −2.05 mm Hg.

Clinical Implications

Recommend potassium-enriched salt substitutes for secondary prevention in appropriate post-stroke patients, with potassium monitoring in those with chronic kidney disease or on RAAS inhibitors.

Limitations

• Open-label cluster design may allow behavioral spillover or measurement biases
• Subgroup analysis within a larger trial; generalizability outside rural China requires caution

Future Directions

Implementation studies in diverse health systems, potassium safety in CKD, and cost-effectiveness analyses for scale-up.