NIH-Funded Trial of HRT, Antioxidants Ends WithoutPromising Results

NIH-Funded Trial of HRT, Antioxidants Ends WithoutPromising Results

SAN FRANCISCO--Postmenopausal women with heart disease areapparently not helped with either hormone replacement therapy (HRT) or high-doseantioxidant supplementation, according to a study sponsored by the NationalHeart, Lung and Blood Institute (NHLBI), an arm of the National Institutes ofHealth (NIH). Researchers from the University of California, San Francisco, whowere led by David D. Waters, M.D., of the university's division of cardiology,found that not only did the women not benefit from either treatment, but theywere actually more prone to adverse coronary events than the women takingplacebo. This study was published in the Nov. 20 issue of the Journal of theAmerican Medical Association (288, 19:2432-40, 2002) (www.jama.com)and presented at the American Heart Association's annual meeting in Chicago onNov. 20.

"This study adds to the growing body of evidence that hormone therapy isnot helpful in the treatment--or in the prevention--of heart disease," saidClaude Lenfant, M.D., NHLBI director, "and it provides new information onthe absence of benefit from high-dose antioxidant vitamins."

Researchers divided 423 postmenopausal women with at least 15 percent to 75percent coronary stenosis at baseline into one of four groups: 1) HRT andplacebo vitamin; 2) hormone placebo and high-dose antioxidants consisting of 800IU/d of vitamin E and 1,000 mg/d of vitamin C; 3) HRT and antioxidants; or 4)placebo. Researchers performed angiograms when women entered the study and atthe study's conclusion three years later. During the trial, women visitedclinics at six- and 12-month intervals to provide an analysis of symptoms andquality of life, as well as to take diagnostic tests that included bloodpressure, pap smear and mammography.

Results indicated the women taking active HRT showed more progression ofcoronary heart disease than women receiving hormone placebo, and women receivingactive vitamins had a similar degree of angiographic change as women receivingplacebo, but significantly more deaths: 14 patients died in the HRT group andeight in the HRT placebo group, and 16 died in the vitamin group and six died inthe vitamin placebo group. Additional study results indicated there were fewcases of breast or other cancers and no differences in the occurrence of cancerbetween the groups.

The Council for Responsible Nutrition (CRN) released a statement in responseto the study, saying these results showed no effects beyond random variations inresponse and that the researchers based their conclusions on statisticallyinsignificant data. "In fact, the actual data showed no difference inartery blockage between the antioxidant group and the control group, even afterthe researchers arbitrarily created 'worst-case' numerical values to fillmissing data points," said John Hathcock, Ph.D., vice president ofnutritional and regulatory science at CRN. "Even those statistics thatwould appear to be significant are, in actuality, the exact pattern that wouldrandomly occur if no treatments had been administered, and as the authors havestated, this could be a 'chance finding.'"

CRN also noted there were several flaws in the study's design. Namely, thestudy groups were not stratified to assure that all the treatment groups weresimilar with respect to the degree of coronary artery blockage, and the studywas not powered to detect differences in clinical outcomes.

CRN cautioned that this study should not be the final word on antioxidantsfor the prevention of cardiovascular disease. "It is the cumulativeknowledge, or the weight of overall evidence, that provides health careprofessionals and consumers with the best scientific guidance," Hathcocksaid. "Over the past 25 years, more than 20 studies involving more than80,000 people have been conducted on vitamins C and E, and on balance these areoverwhelmingly safe nutrients."