• Bruce Neal, Yangfeng Wu, Xiangxian Feng, Ruijuan Zhang, Yuhong Zhang, Jingpu Shi, Jianxin Zhang, Maoyi Tian, Liping Huang, Zhifang Li, Yan Yu, Yi Zhao, Bo Zhou, Jixin Sun, Yishu Liu, Xuejun Yin, Zhixin Hao, Jie Yu, Ka-Chun Li, Xinyi Zhang, Peifen Duan, Faxuan Wang, Bing Ma, Weiwei Shi, Gian Luca Di Tanna, Sandrine Stepien, Sana Shan, Sallie-Anne Pearson, Nicole Li, Lijing L Yan, Darwin Labarthe, and Paul Elliott.
• From the George Institute for Global Health (B.N., M.T., L.H., Y.L., X.Y., J.Y., K.-C.L., G.L.D.T., S. Stepien, S. Shan) and the Centre for Big Data Research in Health (S.-A.P.), University of New South Wales, and George Clinical (N.L.) - all in Sydney; the School of Public Health (B.N., K.-C.L., P.E.), the U.K. Dementia Research Institute (P.E.), the British Heart Foundation Centre for Research Excellence (P.E.), and the NIHR Imperial Biomedical Research Centre (P.E.), Imperial College London, Health Data Research (P.E.), the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (P.E.), and the Medical Research Council Centre for Environment and Health (P.E.) - all in London; Peking University Clinical Research Center, Peking University (Y.W.), the George Institute for Global Health at Peking University Health Science Center (Y.W., M.T., Z.H., X.Z., L.L.Y.), and the Department of Cardiology, Peking University Third Hospital (J.Y.), Beijing, the School of Public Health, Changzhi Medical College, Changzhi (X.F., Z.L., P.D.), the School of Public Health, Xi'an Jiaotong University, Xi'an (R.Z., Y.Y.), the School of Public Health and Management, Ningxia Medical University, Yinchuan (Y. Zhang, Y. Zhao, F.W.), the Department of Evidence-Based Medicine, First Hospital of China Medical University, Shenyang (J. Shi, B.Z., B.M.), the Department of Noncommunicable Disease Prevention and Control, Center for Disease Control of Hebei Province, Shijiazhuang (J.Z., J. Sun, W.S.), the School of Public Health, Harbin Medical University, Harbin (M.T.), the Global Health Research Center, Duke Kunshan University, Kunshan (L.L.Y.), and the School of Health Sciences, Wuhan University, Wuhan (L.L.Y.) - all in China; and the Feinberg School of Medicine, Northwestern University, Chicago (D.L.).
• N. Engl. J. Med. 2021 Sep 16; 385 (12): 1067-1077.

BackgroundSalt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain.MethodsWe conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia.ResultsA total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76).ConclusionsAmong persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).Copyright © 2021 Massachusetts Medical Society.

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