February 19, 2001

UCSD Researchers Find Raloxifene Is Not Associated With Early Cardiovascular Harm And
May Offer Benefit To Women At Increased Cardiovascular Risk

Following a worldwide study of 7,705 postmenopausal women, researchers found that the osteoporosis therapy raloxifene HCl was not associated with early cardiovascular harm, and, in fact, reduced the risk of cardiovascular events by 40 percent in postmenopausal women with osteoporosis who were also at high risk for cardiovascular disease. The findings are published in the February 20 issue of the Journal of the American Medical Association.

Elizabeth Barrett-Connor, M.D.

Elizabeth Barrett-Connor, M.D., professor of Family and Preventive Medicine at the UCSD School of Medicine, and her colleagues evaluated cardiovascular data from the four-year Multiple Outcomes of Raloxifene Evaluation (MORE) clinical trial, an osteoporosis treatment study. Dr. Barrett-Connor was the principle investigator on the MORE study and UCSD was one of 180 sites in 25 countries participating in the study.

The researchers found that four years of raloxifene therapy did not significantly affect the risk of cardiovascular events in the overall MORE study population of over 7,000 postmenopausal women with osteoporosis. However, the study did find that, compared with placebo, raloxifene reduced the risk of cardiovascular events by 40 percent in a subset of 1,035 postmenopausal women with osteoporosis who were also at increased risk for cardiovascular disease. Contrary to recent findings on estrogen therapy, there was no evidence that raloxifene caused an early increase in the risk of cardiovascular events in either the overall MORE population or the high-risk subset.

"These preliminary data are particularly encouraging because final data from the Heart and Estrogen/progestin Replacement Study (HERS) and preliminary data from the Women's Health Initiative (WHI), have suggested an early increase in the risk of cardiovascular events associated with estrogen and hormone replacement therapy," said Dr. Barrett-Connor. "We know that raloxifene—a selective estrogen receptor modulator, or SERM—acts through estrogen receptors in a more selective fashion than estrogen therapy. But we wanted to know if there might be a similar increase in early cardiovascular events.”

“Reassuringly, there was no evidence of early cardiovascular harm with raloxifene in this study. In fact, it appeared there may be a cardiovascular benefit in those women at the greatest risk for cardiovascular disease,” she said.

Completed in 1999, MORE was a randomized, double-blind, placebo-controlled study. Patients were randomly assigned to receive raloxifene 60 mg/d (n=2,557), raloxifene 120 mg/d (n=2,572), or placebo (n=2,576) for four years. The study was funded by Eli Lilly and Company, which markets raloxifene 60 mg/d under the brand name Evistaâ for the prevention and treatment of osteoporosis in postmenopausal women.

Dr. Barrett-Connor and her colleagues used data from MORE to compare the effects of raloxifene versus placebo on the risk of cardiovascular events. Cardiovascular events, collected as adverse events in the MORE trial, were defined as all coronary events (myocardial infarction, unstable angina, or coronary ischemia) and cerebrovascular events (stroke or transient ischemic attack).

The number of cardiovascular events reported in the overall MORE population did not differ significantly among raloxifene and placebo. Because the overall MORE population was at relatively low cardiovascular risk, researchers also explored the effect of raloxifene on cardiovascular events in a subset of 1,035 women at increased cardiovascular risk. In this high-risk subset, 833 women had multiple (3 or more) cardiovascular risk factors and 202 women had established coronary heart disease.

Compared with placebo, a 40 percent reduction in the number of cardiovascular events was observed in this high-risk population. The number of cardiovascular events in the raloxifene treatment was reduced compared with placebo after approximately the first year of treatment.

The high-risk patient population in MORE was identified using the same criteria established for enrolling postmenopausal in the Raloxifene Use for The Heart, or RUTH, study. RUTH, an evidence-based clinical study involving 10,101 women, is designed to determine if raloxifene can reduce the risk of cardiovascular events in postmenopausal women at high risk for heart disease. Preliminary results from the study are expected in approximately five years.

“RUTH is the critical next step to better understanding the results from MORE,” said Barrett-Connor. “When RUTH is complete we will have relevant data on whether raloxifene can provide postmenopausal women with a much-needed preventative option for cardiovascular disease."

In addition to Dr. Barrett-Connor, authors of the MORE four-year cardiovascular study are: Deborah Grady, M.D., University of California, San Francisco; Krzysztof Hoszowski, M.D., Railway Hospital (Poland); Pentti Rautaharju, M.D., Wake Forrest University; and, from Eli Lilly and Company, Pamela W. Anderson, M.D., Kristine D. Harper, M.D., David A. Cox, Ph.D., and Andreas Sashegyi, Ph.D.

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Media Contact:
Kate Deely Smith
619-543-6163
kdeely@ucsd.edu

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