Raloxifene, an oestrogen supplement used to treat osteoporosis, can significantly reduce the risk of cardiovascular problems among post-menopausal women at high risk for acute coronary events and among those with established coronary heart disease, according to new research published in the 20 February issue of the Journal of the American Medical Association (JAMA).
Dr Elizabeth Barrett-Connor of the University of California, San Diego, led a team of researchers who analysed data to determine the effect of raloxifene on cardiovascular events in post-menopausal women with osteoporosis.
The study was a secondary analysis using data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, a randomised, double-blind, placebo-controlled four-year trial designed to determine the effect of raloxifene on bone mineral density and vertebral fractures. A total of 7,705 women with an average age of 67 took part in the MORE trial at 180 sites in 25 countries.
Raloxifene is used to treat osteoporosis, the thinning of the bones with reduction in bone mass caused by depletion of calcium and bone protein. People with osteoporosis are predisposed to fractures that are often slow to heal and heal poorly. Raloxifene alters the cycle of bone formation and breakdown to reduce bone tissue loss.
Raloxifene is widely available under the name Evista, a drug produced by the Eli Lilley pharmaceutical group, and is a selective oestrogen receptor modulator. It has effects similar to oestrogen on some tissues, but inhibits the effects of oestrogen on other tissues.
Raloxifene decreases low-density lipoprotein (LDL) cholesterol, the so-called 'bad' cholesterol. But unlike oestrogen, raloxifene does not increase high density lipoprotein (HDL), the 'good' cholesterol. According to background information cited in the article, raloxifene improves cardiovascular risk factors, but its effect on cardiovascular events is unknown.
A total of 2,557 women in the MORE trial were randomly assigned to receive 60 mg/d of raloxifene. Some 2,572 received a 120-mg daily dose, and 2,576 women received a placebo.
The researchers analysed data on cardiovascular events, including coronary events - myocardial infarction (heart attack), unstable angina (chest pain caused by inadequate oxygen supply to the heart muscle) or coronary ischemia (inadequate blood supply caused by blockage of blood vessels).
They also looked at cerebrovascular events such as stroke (damage to the brain caused by lack of oxygen when blood flow is impaired by blockages, or rupture of an artery to the brain) and transient ischemic attack (a 'mini-stroke' caused by temporary lack of adequate blood and oxygen to the brain with symptoms that resolve within a short period).
"In the overall cohort, there were no significant differences between treatment groups in the number of combined coronary and cerebrovascular events: 96 (3.7 per cent) with placebo, 82 (3.2 per cent) with 60 mg/day of raloxifene and 94 (3.7 per cent) with 120 mg/day of raloxifene," Dr Barrett-Connor said in the article.
Women who took the lower dose of raloxifene had a 14 per cent lower risk of combined events, and those who took the higher dose had a 2 per cent lower risk.
Similar results were obtained when coronary and cerebrovascular events were analysed separately. "Among the subset of 1,035 women with increased cardiovascular risk, those assigned to raloxifene had a significantly lower risk of cardiovascular events compared with the placebo group," Dr Barrett-Connor said. There was a 40 per cent lower risk for both raloxifene groups, she added.
There was no evidence that raloxifene caused an early increase in risk of cardiovascular events, however. "The number of cardiovascular events during the first year was not significantly different across groups in the overall cohort, or among women at increased cardiovascular risk or with evidence of established coronary heart disease," the researchers said.
Further trials are being carried out under the Raloxifene Use for The Heart (RUTH) programme to assess whether raloxifene affects the risk of cardiovascular events in post-menopausal women. The trial involves post-menopausal women with established coronary heart disease (CHD) or with multiple risk factors for acute CHD events. Results will not be available for several years.
"Before raloxifene is used for prevention of cardiovascular events, these findings require confirmation in trials with evaluation of cardiovascular outcomes as the primary objective," the authors concluded.