Raloxifene linked to decreased risk of stroke, TIA: findings based on a subgroup of women at high risk for cardiovascular disease. (Postmenopausal Women).

CHICAGO--Treatment with raloxifene continues to show an ability to protect against cardiovascular events in postmenopausal women, based on additional post hoc analyses of data collected in a large osteoporosis trial.

The cardiovascular findings cannot be used to guide treatment, however, because they're based on a subgroup of women at high risk of cardiovascular disease and because cardiovascular disease protection was not a pre-specified aim of the Multiple Outcomes of Raloxifene Evaluation (MORE) study. But the observation that raloxifene treatment was associated with a dramatic cut in the incidence of stroke, transient ischemic attack (TIA), and coronary disease events was promising--and in stark contrast to the spike in cardiovascular events that has recently been seen in several trials of postmenopausal women treated with estrogen.

"This is a very pleasant surprise and very exciting" Dr. Elizabeth Barrett-Connor said at the annual scientific sessions of the American Heart Association. "Raloxifene may have the cardiovascular disease benefits that we once thought estrogen might have," said Dr. Barrett-Connor, a professor of family and preventive medicine at the University of California, San Diego, and the lead investigator of the cardiovascular disease analysis from the MORE study

Raloxifene is a selective estrogen receptor modulator that was designed to cut fracture risk in postmenopausal women while also reducing their risk of breast cancer. The MORE study and its follow-up analyses have been sponsored by Eli Lilly & Co., the company that markets raloxifene as Evista.

The study enrolled 7,705 postmenopausal women with osteoporosis, and randomized them to raloxifene at 60 mg/day or 120 mg/day or placebo. The women were followed for 3 years, and in 1999 the researchers published results that showed that treatment with either dose of raloxifene led to a significant drop in the occurrence of osteoporotic spine fractures (JAMA 282[7]:637-45, 1999). Raloxifene was approved by the Food and Drug Administration, based on these results, for the prevention of osteoporotic fractures in postmenopausal women.

Dr. Barrett-Connor and her associates then analyzed the MORE data based on cardiovascular events. The outcomes that they used in this analysis were initially reported by the study investigators as adverse events. The available information on these events, collected during 4 years of follow-up, was adjudicated by a cardiologist to increase the likelihood that true cardiovascular events had actually occurred.

The analysis looked at the study population in two different ways. First, the researchers looked at the apparent impact of raloxifene on cardiovascular events, compared with placebo in the entire study population. Second, a high-risk subset of women was identified based on medical history, including factors such as a history of MI or coronary revascularization, diabetes, age, smoking status, blood pressure, and serum lipid levels.