July 12 (Bloomberg) -- Eli Lilly & Co.'s Evista drug may increase the risk of blood clots and fatal stroke in older women, a finding that may discourage its use to prevent bone- thinning osteoporosis in some patients.

Women who took Evista had a 49 percent increase in their risk of dying from stroke compared with those taking a placebo, a study found. Their chance of getting blood clots from use of the drug, known chemically as raloxifene, rose by 44 percent in the research involving 10,101 women in 26 countries.

Patients will have to balance those risks against the protection Evista offers against osteoporosis and breast cancer, said Lori Mosca, director of preventive cardiology at New York Presbyterian Hospital. Women in the study who took Evista were 44 percent less likely to develop breast cancer, a finding that mirrored previous studies.

``Usefulness of this drug in any woman will depend on her personal risk of breast cancer, osteoporosis, stroke and blood clots,'' said Mosca, who co-wrote the study, in a telephone interview today. ``It's not a one-size-fits-all answer.''

The study will be published tomorrow in the New England Journal of Medicine.


Evista was approved in 1997 to prevent osteoporosis, which can lead to fractures. Researchers suspected that it might also have an effect on breast cancer and heart disease, like other drugs that modify the effects of the female hormone estrogen such as tamoxifen.


The most recent study, led by Elizabeth Barrett-Connor of the University of California, San Diego, followed post- menopausal women who had existing heart disease, or risked developing it because of smoking or conditions such as diabetes.


Deaths
After about 5 1/2 years, there was no difference in rates of heart attacks or heart-related hospitalizations and deaths among Evista users and those who received a placebo. While strokes in the treated and untreated group were in the same range, 59 women who took Evista died of the brain illness, compared with 39 women who got a placebo.

Lilly released partial findings from the study April 12, at the request of the U.S. Food and Drug Administration. Lilly said then that while overall stroke rates in the study were low, Evista was associated with ``an increase in stroke mortality.''

Data from the study, including the precise increase in risk of stroke death, were not released because the findings had not yet been reviewed by experts, said Keri McGrath, a Lilly spokeswoman, in a telephone interview today.

Reviewing the Label
Lilly recommended then that doctors consider women's stroke risk when prescribing Evista, and the company is reviewing the drug's label with the FDA, she said.

The label doesn't mention risk of death from stroke. The company has communicated Evista's risks with doctors, pharmacists, other health professionals and patients through its sales force and direct mail, McGrath said.

The breast cancer finding in the most recent study supported the result of a different study, released in June, which said Evista is as effective against breast cancer as tamoxifen, the standard treatment for that disease.

Lilly has said it is planning to apply to the FDA for approval to market the drug as a breast cancer preventative.

Older women with a family history of stroke or high blood pressure should consider using Evista alternatives for osteoporosis, such as Merck & Co.'s Fosamax, when treating patients at elevated stroke risk, the researchers said.

`Cautious Use'
``I'll continue to use it, but will be very cautious about it,'' Mosca said. ``I'll use it in women who stroke risk is not elevated.''

The data is being analyzed further to determine which women may be at highest risk of stroke and blood clots when taking the Lilly drug, Mosca said.

``We have to look at the full spectrum of risks and benefits, especially in the field of prevention where there's only a theoretical risk of developing the disease,'' she said.

To contact the reporters on this story:
John Lauerman in Boston at jlauerman@bloomberg.net
Angela Zimm in Boston at azimm@bloomberg.net
Last Updated: July 12, 2006 17:31 EDT