Antioxidants of No Benefit for Secondary Prevention in Women

CHICAGO — Antioxidant B vitamins and folic acid failed to slow the progression of cardiovascular disease in women at high risk or with established cardiovascular disease, according to results from the WAFACS trial presented at the annual scientific sessions of the American Heart Association.

“These data, along with those from previously published randomized trials, do not support the use of folic acid and B vitamin supplements as preventive agents against cardiovascular disease among those with established vascular disease or those at high risk,” reported Dr. Christine M. Albert of the division of preventive medicine at Brigham and Women's Hospital, Boston.

“The combination of folic acid, vitamin B₆, and vitamin B₁₂ did not reduce risk of total cardiovascular events or any of the individual secondary end points among 5,442 women at high risk for cardiovascular disease over a very long follow-up of 7.3 years,” she said.

In WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), 5,442 female health professionals participating in another randomized trial of antioxidant vitamins (WACS) were randomly assigned to a combination of folic acid (2.5 mg daily), vitamin B₆ (50 mg daily), and vitamin B₁₂ (1 mg daily). These women were considered to be high risk based on either a confirmed history of cardiovascular disease or the presence of at least three cardiovascular disease risk factors, including hypertension, hypercholesterolemia, diabetes, current smoking, body mass index higher than 30 kg/m

After a mean follow-up of 7.3 years, 796 women (14.6%) had a confirmed cardiovascular event. In the intention-to-treat analysis, the cumulative incidence of the primary end point did not differ between those given active folate treatment and those given folate placebo.

“This absence of benefit was observed in all prespecified subgroups including the high-risk primary prevention population,” said Dr. Albert.

The researchers tested whether homocysteine lowering by background folic acid fortification in the food supply, which took effect between 1996 and 1998, might have accounted for the null findings, and found that this was not the case. Homocysteine levels were about 18% lower in the active treatment arm, compared with the placebo arm, but still there was no benefit.

Discussant Dr. Rita F. Redberg considered the question of whether the results of WAFACS can be generalized to men and to the primary prevention setting. If such studies were to be done in those populations, results would be unlikely to differ significantly from those seen in this trial, she said.

“Study after study has failed to find a benefit from dietary supplements, and I think there's just no getting away from an emphasis on a heart-healthy diet and regular physical activity,” concluded Dr. Redberg, director of women's cardiovascular services at the University of California, San Francisco.

CHICAGO — Antioxidant B vitamins and folic acid failed to slow the progression of cardiovascular disease in women at high risk or with established cardiovascular disease, according to results from the WAFACS trial presented at the annual scientific sessions of the American Heart Association.

“These data, along with those from previously published randomized trials, do not support the use of folic acid and B vitamin supplements as preventive agents against cardiovascular disease among those with established vascular disease or those at high risk,” reported Dr. Christine M. Albert of the division of preventive medicine at Brigham and Women's Hospital, Boston.

“The combination of folic acid, vitamin B₆, and vitamin B₁₂ did not reduce risk of total cardiovascular events or any of the individual secondary end points among 5,442 women at high risk for cardiovascular disease over a very long follow-up of 7.3 years,” she said.

In WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), 5,442 female health professionals participating in another randomized trial of antioxidant vitamins (WACS) were randomly assigned to a combination of folic acid (2.5 mg daily), vitamin B₆ (50 mg daily), and vitamin B₁₂ (1 mg daily). These women were considered to be high risk based on either a confirmed history of cardiovascular disease or the presence of at least three cardiovascular disease risk factors, including hypertension, hypercholesterolemia, diabetes, current smoking, body mass index higher than 30 kg/m

After a mean follow-up of 7.3 years, 796 women (14.6%) had a confirmed cardiovascular event. In the intention-to-treat analysis, the cumulative incidence of the primary end point did not differ between those given active folate treatment and those given folate placebo.

“This absence of benefit was observed in all prespecified subgroups including the high-risk primary prevention population,” said Dr. Albert.

The researchers tested whether homocysteine lowering by background folic acid fortification in the food supply, which took effect between 1996 and 1998, might have accounted for the null findings, and found that this was not the case. Homocysteine levels were about 18% lower in the active treatment arm, compared with the placebo arm, but still there was no benefit.

Discussant Dr. Rita F. Redberg considered the question of whether the results of WAFACS can be generalized to men and to the primary prevention setting. If such studies were to be done in those populations, results would be unlikely to differ significantly from those seen in this trial, she said.

“Study after study has failed to find a benefit from dietary supplements, and I think there's just no getting away from an emphasis on a heart-healthy diet and regular physical activity,” concluded Dr. Redberg, director of women's cardiovascular services at the University of California, San Francisco.

CHICAGO — Antioxidant B vitamins and folic acid failed to slow the progression of cardiovascular disease in women at high risk or with established cardiovascular disease, according to results from the WAFACS trial presented at the annual scientific sessions of the American Heart Association.

“These data, along with those from previously published randomized trials, do not support the use of folic acid and B vitamin supplements as preventive agents against cardiovascular disease among those with established vascular disease or those at high risk,” reported Dr. Christine M. Albert of the division of preventive medicine at Brigham and Women's Hospital, Boston.

“The combination of folic acid, vitamin B₆, and vitamin B₁₂ did not reduce risk of total cardiovascular events or any of the individual secondary end points among 5,442 women at high risk for cardiovascular disease over a very long follow-up of 7.3 years,” she said.

In WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), 5,442 female health professionals participating in another randomized trial of antioxidant vitamins (WACS) were randomly assigned to a combination of folic acid (2.5 mg daily), vitamin B₆ (50 mg daily), and vitamin B₁₂ (1 mg daily). These women were considered to be high risk based on either a confirmed history of cardiovascular disease or the presence of at least three cardiovascular disease risk factors, including hypertension, hypercholesterolemia, diabetes, current smoking, body mass index higher than 30 kg/m

After a mean follow-up of 7.3 years, 796 women (14.6%) had a confirmed cardiovascular event. In the intention-to-treat analysis, the cumulative incidence of the primary end point did not differ between those given active folate treatment and those given folate placebo.

“This absence of benefit was observed in all prespecified subgroups including the high-risk primary prevention population,” said Dr. Albert.

The researchers tested whether homocysteine lowering by background folic acid fortification in the food supply, which took effect between 1996 and 1998, might have accounted for the null findings, and found that this was not the case. Homocysteine levels were about 18% lower in the active treatment arm, compared with the placebo arm, but still there was no benefit.

Discussant Dr. Rita F. Redberg considered the question of whether the results of WAFACS can be generalized to men and to the primary prevention setting. If such studies were to be done in those populations, results would be unlikely to differ significantly from those seen in this trial, she said.

“Study after study has failed to find a benefit from dietary supplements, and I think there's just no getting away from an emphasis on a heart-healthy diet and regular physical activity,” concluded Dr. Redberg, director of women's cardiovascular services at the University of California, San Francisco.