Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial.
What this study found
The folic acid and B vitamin combination did not reduce major cardiovascular events or total mortality in this high-risk women’s trial. In the active arm versus placebo, combined major cardiovascular disease occurred in 406 (14.9%) versus 390 (14.3%) participants (RR 1.03, 95% CI 0.90-1.19; P = .65), and total mortality was 250 (9.2%) versus 256 (9.4%) (RR 0.97, 95% CI 0.81-1.15; P = .73). Myocardial infarction, stroke, coronary revascularization, cardiovascular death, and the composite of myocardial infarction, stroke, and cardiovascular death were also not significantly different.…
- Study & population
- Randomized, placebo-controlled trial in female health professionals in the United States who were age 40 years or older, postmenopausal or not intending pregnancy, and had prior cardiovascular disease or at least 3 cardiac risk factors.
- Intervention
- Women in the active intervention arm received a daily combination pill containing folic acid 2.5 mg, vitamin B6 50 mg, and vitamin B12 1 mg for about 7 years, compared with placebo.
- Key limitation
- The trial was conducted in women at high cardiovascular risk, so findings may not generalize beyond this population.
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Open PDFOriginal abstract
CONTEXT Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials. OBJECTIVE To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD. DESIGN, SETTING, AND PARTICIPANTS Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005. INTERVENTION Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12. MAIN OUTCOME MEASURES A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality. RESULTS Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L). CONCLUSION After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000541.