Women's Antioxidant and Folic Acid Cardiovascular Study - WAFACS

Description:

The goal of the trial was to evaluate the effect of treatment with folic acid and vitamin B compared with placebo among women with or at increased risk for cardiovascular (CV) disease.

Hypothesis:

Folic acid and vitamin B will be more effective in preventing major adverse cardiac events among high-risk women.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Factorial

Patients Screened: 53,788
Patients Enrolled: 5,442
Mean Follow Up: 7.3 years
Mean Patient Age: 63 years
Female: 100

Patient Populations:

Women ages ≥40 years with pre-existing CV disease or ≥3 coronary risk factors

Exclusions:

• History of cancer
• History of a serious non-CV disease
• Currently taking Coumadin or another anticoagulant

Primary Endpoints:

Composite of CV death, MI, stroke, or revascularization

Secondary Endpoints:

Individual components of the composite outcome

Drug/Procedures Used:

Patients were randomized in a double-blind manner to active treatment with folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) (n = 2,721) or placebo (n = 2,721). The trial was part of the larger WACS trial in which patients were randomized in a factorial manner to vitamin C, vitamin E, and beta-carotene.

Concomitant Medications:

At baseline (for vitamin vs. placebo), the use of aspirin was 51.1% vs. 48.9%, hormone therapy was 48.5% vs. 48.8%, lipid-lowering drugs were 33.6% vs. 34.5%, beta-blockers were 26.6% vs. 27.0%, angiotensin-converting enzyme inhibitors were 24.3% vs. 25.8%, and multivitamins were 22.6% vs. 23.2%, respectively.

Principal Findings:

There was no difference in the primary composite endpoint of CV death, myocardial infarction (MI), stroke, or revascularization through a mean of 7-year follow-up between active treatment and placebo (14.9% vs. 14.3%, p = 0.65). There was also no difference among the individual components of the composite, including CV death (3.5% vs. 3.5%, p = 0.93), MI (2.4% vs. 2.7%, p = 0.42), stroke (2.9% vs. 2.5%, p = 0.44), or revascularization (9.3% vs. 9.4%, p = 0.87), for active versus placebo, respectively.

Due to introduction of folic acid fortification into the food supply during the study, folic acid levels in the subgroup of patients with blood samples increased from baseline to end of study not only in the active treatment group (8.9-39.6 ng/ml, p < 0.001), but also to a lesser degree in the placebo group (8.8-15.4 ng/ml, p < 0.001). However, homocysteine levels were not reduced in the placebo group (12.5 µmol/L at baseline and 11.8 µmol/L at follow-up), but were reduced in the active treatment group (from 12.1 µmol/L at baseline to 9.8 µmol/L at study end, p < 0.001).

Interpretation:

Among women with or at increased risk for CV disease, treatment with folic acid and vitamin B were not associated with differences in the composite primary endpoint of CV death, MI, stroke, or revascularization through a mean of 7-year follow-up compared with placebo.

Results were similar in all of the prespecified subgroups, including patients with established CV disease as well as those at risk for coronary disease. While folic acid levels increased in the placebo group, likely due to introduction of folic acid fortification into the food supply, the increase was not enough to modify homocysteine levels. Despite reductions in homocysteine levels with active therapy, no corresponding reductions in clinical events were observed. Data from the present study are similar to those in the HOPE-2 trial, which showed no benefit with folic acid or vitamin B among patients with pre-existing CV disease or diabetes, and the NORVIT trial, which showed no benefit with folic acid or vitamin B for post-MI care.

References:

Albert CM, Cook NR, Gaziano JM, et al. 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. JAMA 2008;299:2027-2036.

Presented by Dr. Christine Albert at the American Heart Association Annual Scientific Sessions, Chicago, IL, November 2006.

Clinical Topics: Statins

Keywords: Stroke, Myocardial Infarction, Vitamin E, Follow-Up Studies, beta Carotene, Food Supply, Risk Factors, Vitamin B 12, Vitamin B 6, Folic Acid, Diabetes Mellitus


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