The study looked at 20,702 adults with hypertension but without history of stroke or heart attack. The researchers from Peking University First Hospital in Beijing compared the impact of a daily single pill containing 10 mg of the blood-pressure reduction medication enalapril and 0.8 mg folic acid with a daily pill of 10 mg enalapril alone for an average treatment time of 4.5 years.
During this treatment period, 282 participants (2.7%) in the enalapril-folic acid group had their first stroke compared to 355 participants (3.4%) in the enalapril group.
The results, published in the Journal of the American Medical Association (JAMA), found this equated to an absolute risk reduction of 0.7% and a relative risk reduction of 21%.
They also found significant reductions in the risk of ischemic stroke in the enalapril-folic acid group compared to the enalapril group (2.2% vs 2.8%) as well as composite cardiovascular events like cardiovascular death, heart attack and stroke (3.1% vs 3.9%).
In contrast, they found no significant difference between the groups for the risk of hemorrhagic stroke, heart attack, all-cause death or in the frequencies of adverse events.
The researchers said that baseline folate levels were important in these outcomes, with the potential benefit being more pronounced in those with lower starting folate levels.
Yet the authors wrote: "We speculate that even in countries with folic acid fortification and widespread use of folic acid supplements such as in the United States and Canada, there may still be room to further reduce stroke incidence using more targeted folic acid therapy - in particular, among those with the TT genotype and low or moderate folate levels."
The researchers looked at the impact of methylenetetrahydrofolate reductase (MTHFR) variants – the main regulatory enzyme for folate metabolism which can lead to a reduction in enzyme activity and therefore decreased folate levels.
They said the TT genotype, a variant of MTHFR, leads to a 60% reduction in the enzyme function. This variant is present in all populations but can vary in frequency.
They said these were important findings in an area which was otherwise “not well established”.The China Stroke Primary Prevention Trial (CSPPT), conducted from May 2008 to August 2013 in 32 communities in the Jiangsu and Anhui provinces, was unprecedented among primary stroke prevention trials in its total of 637 stroke events.
Published online ahead of print, doi:10.1001/jama.2015.2274
“Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China”
Authors: Y. Huo, J. Li, X. Qin, Y. Huang, X. Wang, R. F. Gottesman, G. Tang, B. Wang et al.