Abstract 5062: Effect of Folic Acid and B Vitamins on the Occurrence of Venous Thromboembolism: a Randomized Trial in Women at High Cardiovascular Risk
Background: Elevated homocysteine levels are associated with increased risk of venous thromboembolism (VTE) in observational studies, but it remains unclear whether lowering homocysteine through supplementation with folic acid and B vitamins reduces risk.
Methods: Within an ongoing randomized trial of antioxidant vitamins, the Women’s Antioxidant and Folic Acid Cardiovascular Disease Study (WAFACS) tested in a randomized, placebo-controlled design whether a combination pill of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d) would reduce the risk of cardiovascular events. WAFACS randomized 5,442 women who were US health professionals aged 42 years or older, with either a history of cardiovascular disease or 3 or more coronary risk factors. Documented VTE (deep vein thrombosis or pulmonary embolism) and unprovoked VTE (no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated as secondary endpoints.
Results: VTE occurred in 132 women (60 in the active group and 72 in the placebo group) during a randomized treatment period of 7.3 years. The incidence of VTE (per 1,000 person-years) was 3.18 in the active group compared with 3.85 in the placebo group (relative hazard 0.82; 95% confidence interval (CI): 0.59 –1.16; P=0.27). The observed reduction was somewhat stronger, but still not significant, in analyses confined to 86 unprovoked events (relative hazard 0.68; CI: 0.44 –1.04; P=0.075). In subgroup analyses, we found a significant interaction between treatment and body mass index (P=0.044). Among 2,690 obese women (body mass index ≥ 30 kg/m2), the relative hazard was 0.57 (CI: 0.36 – 0.91; P=0.019), comparing the active and placebo groups. In a blood substudy of 300 participants, geometric mean plasma homocysteine level was decreased by 2.3 μmol/L in the active treatment group over that observed in the placebo group, an amount consistent with a modest reduction in VTE risk in a recent meta-analysis of observational studies.
Conclusion: A combination pill of folic acid, vitamin B6, and vitamin B12 was associated with a modest, non-significant reduction in risk of VTE that was consistent with observational studies.