The RUTH ( Raloxifene Use for The Heart ) trial is a randomized, placebo-controlled, double-blind trial designed to determine whether Raloxifene 60 mg/day compared with placebo lowers the risk of coronary events ( coronary death, nonfatal myocardial infarction, or hospitalized acute coronary syndromes other than myocardial infarction ) and reduces the risk of invasive breast cancer in women at risk for a major coronary event.

Raloxifene ( Evista ) is a selective estrogen receptor modulator ( SERM ).

Between June 1998 and August 2000, 10,101 women were enrolled.
Approximately half of the women had documented coronary heart disease ( CHD ) ( n = 5,031 ); the remainder had multiple CHD risk factors that increased their risk for a CHD event ( n = 5,070 ). The mean age of participants was 68 years ( 39% were >70 years old ), and did not differ between those with documented CHD and those at increased CHD risk.
Most women were Caucasian ( 84% ); 60% had a body mass index ( BMI ) >/=27 kg/m(2), 46% had diabetes mellitus, 78% had systemic hypertension, and 14% had low-density lipoprotein cholesterol >160 mg/dl.
Compared with women at increased CHD risk, women with documented coronary heart disease had higher cardiovascular risk scores, a higher prevalence of abnormal electrocardiograms, greater use of cardiovascular medications, were more likely to have had cardiac rehabilitation, and were more likely to have previously used estrogen or oral contraceptives, but had a slightly lower prevalence of CHD risk factors such as smoking, obesity, diabetes mellitus, and systemic hypertension, and had lower serum levels of total and low-density lipoprotein cholesterol.

When the MORE trial results became known, invasive breast cancer was added as a second primary outcome.

The women were followed-up for a median of 5.6 years.

As compared with placebo, Raloxifene had no significant effect on the risk of primary coronary events ( 533 vs. 553 events; hazard ratio, HR = 0.95 ), and it reduced the risk of invasive breast cancer ( 40 vs. 70 events; HR= 0.56; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year ); the benefit was primarily due to a reduced risk of estrogen-receptor–positive invasive breast cancers.

There was no significant difference in the rates of death from any cause or total stroke, but Raloxifene was associated with an increased risk of fatal stroke ( 59 vs. 39 events; HR = 1.49; absolute risk increase, 0.7 per 1000 woman-years ) and venous thromboembolism ( 103 vs. 71 events; HR = 1.44; absolute risk increase, 1.2 per 1000 woman-years ).

Raloxifene reduced the risk of clinical vertebral fractures ( 64 vs. 97 events; HR = 0.65; absolute risk reduction, 1.3 per 1000 ).

“ Raloxifene did not significantly affect the risk of coronary heart disease. The benefits of Raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke, “ the authors conclude.

Source: The New England Journal of Medicine, 2006


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