Bone Drug Lowers Risk of Heart Disease

By William J. Cromie

Gazette Staff

A drug approved to treat osteoporosis, and that may prevent breast cancer, has been found by Harvard researchers to lower risk of heart disease in older women.

Tested on postmenopausal women, raloxifene lowered harmful cholesterol and fibrogen, a protein associated with premature hardening of the arteries. However, the drug does not reduce risk factors as much as hormone replacement therapy.

Nevertheless, "this is good news for millions of postmenopausal women facing the difficult dilemma of whether or not to take hormone supplements," says Brian Walsh, assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School. "Raloxifene, which mimics estrogen in some tissues while blocking the hormone in others, is clearly an important option for those women not looking to alleviate the symptoms of menopause but rather to reduce their risk factors for diseases such as heart disease and osteoporosis."

Estrogen replacement is believed to protect against osteoporosis and heart disease, but also is believed to increase the risk of breast and uterine cancer. In their six-month study of 390 postmenopausal women, Walsh and his colleagues did not look at the risk of breast cancer. They also did a one-year study to check for signs of uterine cancer, but no results are available yet.

About half of postmenopausal women discontinue treatment with estrogen and progestin hormones within a year because of concerns about breast and uterine cancer, vaginal bleeding, and breast tenderness. In the study, raloxifene did not cause vaginal bleeding or breast tenderness.

"Hot flashes were the most common side effect found in the raloxifene group, but few women quit the group because of them," notes Walsh, who also heads the Menopause Center at Brigham and Women's Hospital in Boston.

Raloxifene has been approved only for treatment of osteoporosis, and the results of this latest study aren't conclusive enough to show it to be a good alternative for hormone therapy.

Walsh and his colleagues reported these results yesterday in the Journal of the American Medical Association. In an editorial in the same issue, Basil Rifkind and Jacques Rossouw of the National Heart, Lung, and Blood Institute refer to raloxifene as "a designer drug, not yet suitable for everyday wear."

Walsh admits that "this point is well-taken; there's still a lot we don't know about raloxifene. However, the drug significantly lowers LDL [low density or "bad"] cholesterol by 12 percent, comparable to the 14 percent reduction with hormone therapy. Previous studies suggest that such a reduction, if sustained over time, might lower the incidence of heart disease by as much as 18 percent."

Raloxifene also lowered fibrogen, a protein that can cause blood clots, by 12 to 14 percent, while hormone therapy had no effect.

On the other hand, hormone replacement increased levels of "good" cholesterol 11 percent, while raloxifene had no impact. Hormones decreased a substance (plasmogen activator inhibitor-1) that interferes with dissolving blood clots by 29 percent, whereas raloxifene had no effect. Hormones increase blood fats called tryglycerides by 20 percent, while raloxifene showed no change.

Such results don't offer much help to women trying to decide whether to start or stop hormone replacement therapy. Neither does Walsh's statement that "more studies are needed to determine just how effective raloxifene is at protecting against heart disease."

The drug is also being investigated as a way to prevent breast cancer. Preliminary studies show that it can do that, at least in the short term. The heavily publicized drug tamoxifen also shows promise as a preventative, but it raises the risk of uterine cancer. Raloxifene, on the other hand, does not appear to increase the risk of uterine cancer.

Raloxifene, therefore, holds out the promise of preventing breast cancer, lowering the risk of heart disease, and preventing osteoporosis. If it lives up to that promise, it will surely be a miracle drug.