TY - JOUR
T1 - Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China
T2 - The CSPPT randomized clinical trial
AU - for the Csppt Investigators
AU - Huo, Yong
AU - Li, Jianping
AU - Qin, Xianhui
AU - Huang, Yining
AU - Wang, Xiaobin
AU - Gottesman, Rebecca F.
AU - Tang, Genfu
AU - Wang, Binyan
AU - Chen, Dafang
AU - He, Mingli
AU - Fu, Jia
AU - Cai, Yefeng
AU - Shi, Xiuli
AU - Zhang, Yan
AU - Cui, Yimin
AU - Sun, Ningling
AU - Li, Xiaoying
AU - Cheng, Xiaoshu
AU - Wang, Jian'An
AU - Yang, Xin Chun
AU - Yang, Tianlun
AU - Xiao, Chuanshi
AU - Zhao, Gang
AU - Dong, Qiang
AU - Zhu, Dingliang
AU - Wang, Xian
AU - Ge, Junbo
AU - Zhao, Lianyou
AU - Hu, Dayi
AU - Liu, Lisheng
AU - Hou, Fan Fan
AU - Cao, Kejiang
AU - Chen, Luyuan
AU - Gao, Pingjin
AU - Gao, Runlin
AU - Ji, Xunming
AU - Li, Nanfang
AU - Ma, Changsheng
AU - Wang, Wen
AU - Yang, Xinchun
AU - Dai, Xiaohua
AU - Fan, Fangfang
AU - Gao, Xianbin
AU - Hui, Rutai
AU - Jiang, Hua
AU - Jiang, Jiandong
AU - Jiang, Xiaodong
AU - Kong, Wei
AU - Liu, Bin
AU - Sun, Guoping
PY - 2015/4/7
Y1 - 2015/4/7
N2 - Importance: Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. Objective: To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. Design, Setting, and Participants: The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke ormyocardial infarction (MI) participated in the study. Interventions: Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10mg, and folic acid, 0.8mg (n = 10 348) or a tablet containing enalapril, 10mg, alone (n = 10 354). Main Outcomes and Measures: The primary outcomewas first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. Results: During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7%of participants in the enalapril-folic acid group vs 3.4%in the enalapril alone group; hazard ratio [HR], 0.79; 95%CI, 0.68-0.93), first ischemic stroke (2.2%with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95%CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95%CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95%CI, 0.65-1.34), MI (HR, 1.04; 95%CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95%CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. Conclusions and Relevance: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.
AB - Importance: Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. Objective: To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. Design, Setting, and Participants: The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20 702 adults with hypertension without history of stroke ormyocardial infarction (MI) participated in the study. Interventions: Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10mg, and folic acid, 0.8mg (n = 10 348) or a tablet containing enalapril, 10mg, alone (n = 10 354). Main Outcomes and Measures: The primary outcomewas first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. Results: During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7%of participants in the enalapril-folic acid group vs 3.4%in the enalapril alone group; hazard ratio [HR], 0.79; 95%CI, 0.68-0.93), first ischemic stroke (2.2%with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95%CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95%CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95%CI, 0.65-1.34), MI (HR, 1.04; 95%CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95%CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. Conclusions and Relevance: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.
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U2 - 10.1001/jama.2015.2274
DO - 10.1001/jama.2015.2274
M3 - Article
C2 - 25771069
AN - SCOPUS:84927534831
SN - 0098-7484
VL - 313
SP - 1325
EP - 1335
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 13
ER -