The Women's Antioxidant Cardiovascular Study: design and baseline characteristics of participants.
BACKGROUND
The evidence for a potential benefit of antioxidant vitamins and folic acid in cardiovascular disease (CVD) prevention is derived from laboratory, clinical, and observational epidemiological studies but remains inconclusive. Large-scale randomized trials with clinical end points are necessary to minimize confounding and provide unbiased estimates of the balance of benefits and risks, yet data from such trials are scarce, especially among women.


METHODS
The Women's Antioxidant Cardiovascular Study (WACS) is a randomized, double-blind, placebo-controlled trial testing whether antioxidant vitamins and a folic acid/vitamin B(6)/vitamin B(12) combination prevent future cardiovascular events among women with preexisting CVD or >or=3 CVD risk factors. This paper describes the design of the trial and baseline characteristics of participants, evaluates the success of randomization, and addresses the generalizability of future findings.


RESULTS
In a factorial design, 8171 U.S. female health professionals aged >or=40 years were randomized to vitamin E, vitamin C, beta-carotene, or placebos. Of these women, 5442 were also subsequently randomized to folic acid/vitamin B(6)/vitamin B(12) or placebo. The randomization was successful, as evidenced by similar distributions of baseline demographic, health, and behavioral characteristics across treatment groups. The clinical profile of participants was similar to that observed in another large trial of women with CVD.


CONCLUSIONS
The similar distribution of known potential confounders across treatment groups provides reassurance that unmeasured or unknown potential confounders are also equally distributed. Although a definitive conclusion regarding generalizability requires additional trials in diverse populations, there is little biological basis for supposing that the benefit-risk balance differs in other high-risk women.
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. sbassuk@rics.bwh.harvard.edu
Shari S
SS
Bassuk
Christine M
CM
Albert
Nancy R
NR
Cook
Elaine
E
Zaharris
Jean G
JG
MacFadyen
Eleanor
E
Danielson
Martin
M
Van Denburgh
Julie E
JE
Buring
Joann E
JE
Manson
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D009726:Nurses; D018579:Patient Selection; D010919:Placebos; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage*; D016387:Women's Health
D000975:Antioxidants; D010919:Placebos; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12