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Results From the Women's Antioxidant Cardiovascular Study

Nancy R. Cook, ScD; Christine M. Albert, MD; J. Michael Gaziano, MD; Elaine Zaharris, BA; Jean MacFadyen, BA; Eleanor Danielson, MIA; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH

Arch Intern Med. 2007;167(15):1610-1618.

Background  Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD.

Methods  The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005.

Results  A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03).

Conclusion  There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.

Trial Registration  clinicaltrials.gov Identifier: NCT00000541

Author Affiliations: Divisions of Preventive Medicine (Drs Cook, Albert, Gaziano, Buring, and Manson and Mss Zaharris, MacFadyen, and Danielson), Cardiovascular Medicine (Drs Albert, Gaziano, and Buring), and Aging (Drs Gaziano and Buring), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston (Drs Cook, Buring, and Manson); Veterans Affairs Boston Healthcare System (Dr Gaziano); and Department of Ambulatory Care and Prevention, Harvard Medical School, Boston (Dr Buring).

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