Study Confirms Folic Acid, B Vitamins Do Not Prevent Cardiovascular Events

November 14, 2006

November 14, 2006 (Chicago, IL) - Yet another study has shown no benefit of folic acid and B vitamins in the secondary prevention of cardiovascular events [1]. Dr Christine M Albert (Brigham and Women's Hospital, Boston, MA) reported the findings of the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) in a late-breaking clinical-trial session here today. There was no benefit of the supplements in a subgroup of high-risk primary-prevention patients either.

The hypothesis that folic-acid/vitamin-B supplementation leads to a reduction in homocysteine and a subsequent lowering of cardiovascular events has already been declared "dead" as a result of a number of randomized studies that failed to show any benefit, including HOPE-2, NORVIT, and VISP.

"At this point, all of the data suggest that taking folic acid and B vitamins specifically to prevent heart disease is not effective, and if you are taking them just for cardiovascular-disease prevention, you may want to stop," Albert told a press conference. However, she emphasized that there has been no suggestion of harm in any of the studies and that there are other noncardiac reasons to take these supplements.

Albert and colleagues were also able to examine the effect of folic-acid fortification of foods in the US because baseline blood samples were taken from the women before the mandate to fortify foods, during the late 1990s. Fortification did not appear to account for the null findings in their study.

No difference between groups in any of the end points

WAFACS was a randomized controlled study comparing the effects of placebo with a daily combination of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12--the same regimen used in HOPE-2--in reducing the risk of major cardiovascular events over seven years in 5442 female health professionals participating in the larger Women's Antioxidant Cardiovascular Study (WACS).

Participants were over the age of 40, and two thirds of them had a history of CVD; the remainder had three or more risk factors (high-risk primary-prevention subgroup).

The primary end point was a combined outcome of MI, stroke, revascularization, or cardiovascular death. Over an average of 7.29 years of follow-up, there was no difference in the primary end point between the active-treatment group and those receiving placebo (RR 1.03; p=0.65), nor was there any difference between the two groups in any of the secondary end points.

WAFACS: Secondary end points

Primary outcome and its components

Active (n=2721)

Placebo (n=2721)

RR*

p

Combined major CVD

406

390

1.03

0.65

MI

65

74

0.87

0.42

Stroke overall

79

69

1.14

0.44

Ischemic

69

62

1.10

0.57

Hemorrhagic

10

6

1.65

0.33

Revascularization

253

255

0.99

0.87

CABG

87

98

0.88

0.38

PCI

192

177

1.08

0.46

CVD death

96

94

1.01

0.93

Total mortality

147

152

0.96

0.72

*Estimated from Cox-proportional hazard models controlling for age and antioxidant vitamin-treatment assignments

Fortification of food does not explain absence of benefit

When they tried to tease out the effects of fortifying food with folic acid in a subsample of 300 participants, the researchers found that there was an increase in folic-acid concentration in the placebo group as a result of fortification, but this increase was not sufficient to affect homocysteine levels, which were identical in the placebo group at baseline and at the end of follow-up.

In contrast, those in the active-treatment group had much higher folic-acid levels at the end of follow-up, translating into 18% lower homocysteine levels (10.0 µmol/L at the end of the study compared with 12.2 µmol/L at baseline; p<0.001), but this still did not translate into any benefit in terms of CVD.

This seems to support the idea that homocysteine is a marker for preexisting CVD rather than a risk factor in itself, Albert said.

Will the AHA changes guidelines?

The discussant of the study, Dr Rita F Redberg (University of California, San Francisco), said that the study was valid and that it provided a definitive answer to the question posed. But whether this will change behavior is a different matter, she said.

"People are given a false sense of security by taking vitamins, which cost money, and then thinking they don't need to eat healthily or do exercise," she lamented.

"We have learned an important lesson. One is reminded of what we learned from HRT--the importance of randomized clinical trials to test hypotheses generated by experimental and observational data." She added that it was "likely" that the AHA will change their guidelines on folic acid and B vitamins as a result of this and other studies.

  1. Albert C. A randomized trial of folic acid and B-vitamins in the secondary prevention of cardiovascular events in women: Results from the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS). American Heart Association 2006 Scientific Sessions; November 13, 2006; Chicago, IL. PS.03.Late-Breaking Clinical Trials I.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

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