Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers

doi:10.1212/WNL.0000000000003909

Meta-Analysis

. 2017 May 9;88(19):1830-1838.

doi: 10.1212/WNL.0000000000003909. Epub 2017 Apr 12.

Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers

Min Zhao¹, Guangliang Wu¹, Youbao Li¹, Xiaobin Wang¹, Fan Fan Hou¹, Xiping Xu¹, Xianhui Qin², Yefeng Cai²

Affiliations

¹ From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
² From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. pharmaqin@126.com caiyefeng@126.com.

PMID: 28404799
DOI: 10.1212/WNL.0000000000003909

Meta-Analysis

Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers

Min Zhao et al. Neurology. 2017.

. 2017 May 9;88(19):1830-1838.

doi: 10.1212/WNL.0000000000003909. Epub 2017 Apr 12.

Authors

Min Zhao¹, Guangliang Wu¹, Youbao Li¹, Xiaobin Wang¹, Fan Fan Hou¹, Xiping Xu¹, Xianhui Qin², Yefeng Cai²

Affiliations

¹ From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
² From the National Clinical Research Study Center for Kidney Disease (M.Z., Y.L., F.F.H., X.X., X.Q.), State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University; Second Clinical Medical College of Guangzhou University of Chinese Medicine (G.W.), Guangdong, China; Department of Population, Family, and Reproductive Health (X.W.), Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and Department of Neurology (M.Z., Y.C.), Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. pharmaqin@126.com caiyefeng@126.com.

PMID: 28404799
DOI: 10.1212/WNL.0000000000003909

Abstract

Objective: To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials.

Methods: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model.

Findings: Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84-0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67-0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90-1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77-0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90-1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69-0.88) or low baseline vitamin B₁₂ levels (<384 pg/mL: 0.78, 0.68-0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B₁₂, a low prevalence of statin use, but a high prevalence of hypertension.

Conclusions: Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B₁₂ levels.

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Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers

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Meta-analysis of folic acid efficacy trials in stroke prevention: Insight into effect modifiers

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