Raloxifene and Cardiovascular Events

American Heart Association
Tuesday, 19 February 2002

The Multiple Outcomes of Raloxifene Evaluation randomized trial (MORE), a study published in the February 20, 2002 issue of the JAMA, found that the risk of cardiovascular events was not significantly altered in a study of 7,705 postmenopausal women that tested the drug raloxifene (Evista) to treat their osteoporosis. Cardiovascular events were defined as heart attack, stroke, unstable angina or coronary ischemia. However, the study also found that in a subset of women previously diagnosed with cardiovascular disease, the risk of suffering an event was decreased by 40 percent.

"This study adds yet another facet to the discussion of which therapies may be useful to reduce the increased risk of heart attack, stroke and other cardiovascular events faced by postmenopausal women," says Rose Marie Robertson, M.D., immediate-past president of the American Heart Association and medical director of the Vanderbilt University's Women's Heart Institute, in Nashville.

As for raloxifene, she says, "These results are intriguing, but we agree with the authors of the MORE trial that more study is needed before we can conclude what effect raloxifene may have on cardiovascular risk.

"In the meantime, the American Heart Association advises that all women take control of their risk factors such as smoking, high blood pressure, elevated blood cholesterol, obesity and diabetes, through lifestyle changes - increasing physical activity and healthful eating, and medication when needed.

"For women who don't have cardiovascular disease at menopause, the evidence is not yet conclusive enough for us to advise them to take this new agent to prevent heart disease. For women with diagnosed heart disease, we do not recommend starting hormone replacement therapy after menopause," says Robertson, "but we do have many other options that do work."

Raloxifene is a "designer drug" defined as a selective estrogen receptor modulator, or SERM. That means it behaves somewhat like estrogen, but with key differences. It appears to lower LDL cholesterol (low-density lipoproteins or "bad cholesterol"), which can lessen the risk of heart disease. However, unlike estrogen, it does not appear to affect the uterus or breasts. It is used to treat osteoporosis, the thinning of the bones that sometimes follows menopause in women. Unlike estrogen and other medications, it does not increase HDL cholesterol (high-density lipoproteins or "good cholesterol").

Recent studies have begun to clarify the issue of whether hormone replacement therapy can decrease the risk of heart attack, stroke and other cardiovascular events in postmenopausal women. The influential Heart and Estrogen/progestin Replacement Study (HERS) found that in women with cardiovascular disease, initiating hormone replacement therapy with the most common agents at menopause increased their risk of a cardiovascular event over the first year, and did not reduce it later. This would appear to be the same subgroup that benefited from raloxifene in the MORE trial.

For women who have no evidence of cardiovascular disease, other studies suggested a decreased risk of cardiovascular events in women taking hormone replacement therapy (HRT), but these were not placebo-controlled, randomized studies such as HERS. The first large, randomized controlled trials of HRT in these women are being conducted (the NHLBI's Women's Health Initiative and the European WISDOM trial). Results will not be available until 2006.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org