Raloxifene Use for The Heart - RUTH
The goal of the trial was to evaluate treatment with raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer among postmenopausal women with CHD or risk factors for CHD.
Patients Enrolled: 10,101
Mean Follow Up: Median 5.6 years
Mean Patient Age: Mean age 67.5 years
Age ≥55 years, ≥1 year postmenopausal, and established CHD or at increased risk for CHD
MI, coronary artery bypass grafting, or percutaneous coronary intervention within 3 months before randomization; a history of cancer or venous thromboembolism; a life expectancy of <5 years; unexplained uterine bleeding within 6 months; New York Heart Association class III or IV heart failure; chronic liver or renal disease; use of oral or transdermal estrogens within 6 months before randomization; or current use of other sex hormones or selective estrogen receptor modulators
1) Coronary events, defined as a composite of death from coronary causes, myocardial infarction (MI), or hospitalization for an acute coronary syndrome other than MI; and 2) invasive breast cancer
Stroke, venous thromboembolic events, all breast cancers, clinical vertebral fractures, death from coronary causes, death from cardiovascular causes, and death from any cause
Patients were randomized to either raloxifene (60 mg daily; n = 5,044) or placebo (n = 5,057). Patients were followed for a median of 5.6 years.
At baseline, 39% of patients were age ≥70 years and 14% had prior use of estrogen therapy. The average postmenopausal years was 19 years. Diabetes was present in 46% of patients. Cardiovascular risk score was 7.9 in the raloxifene group and 7.8 in the placebo group.
The primary endpoint of coronary events did not differ between treatment groups (2.06% per year for raloxifene vs. 2.16% per year for placebo, hazard ratio [HR] 0.95, p = 0.40). The coprimary endpoint of invasive breast cancer was lower in the raloxifene group compared with placebo (0.15% per year vs. 0.27% per year, HR 0.56, p = 0.003), driven by a reduction in estrogen-receptor–positive invasive breast cancer (0.09% per year vs. 0.21% per year, p < 0.001).
The incidence of clinical vertebral fractures was lower in the raloxifene group compared with placebo (0.24% per year vs. 0.37% per year, p = 0.007), but there was no difference in clinical nonvertebral fractures (1.67% per year vs. 1.73% per year, p = 0.59). There was no difference in death (2.07% per year for raloxifene vs. 2.25% per year for placebo, p = 0.16) or stroke (0.95% per year for raloxifene vs. 0.86% per year for placebo, p = 0.30). Venous thromboembolic events were higher in the raloxifene group (0.39% per year vs. 0.27% per year, HR 1.44, p = 0.02), as was fatal stroke (n = 59 vs. n = 39, HR 1.49, p = 0.05).
Among postmenopausal women with CHD or risk factors for CHD, treatment with raloxifene was not associated with a difference in coronary events compared with placebo, but was associated with a reduction in invasive breast cancer at a median 5.6-year follow-up.
While raloxifene was associated with a reduction in invasive breast cancer, there were increases in fatal stroke and venous thromboembolic events associated with raloxifene. The risk-benefit profile should be considered prior to initiating raloxifene therapy for primary prevention.
Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006;355:125-37.
Presented by P. Collins, European Society of Cardiology Scientific Congress, September 2006.
Clinical Topics: Prevention
Keywords: Stroke, Follow-Up Studies, Raloxifene, Estrogens, Breast Neoplasms, Coronary Disease, Risk Factors, Risk Assessment, Selective Estrogen Receptor Modulators, Diabetes Mellitus, Primary Prevention
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