Raloxifene Use for The Heart - RUTH

Description:

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.

Study Design

Study Design:

Patients Enrolled: 10,101
Mean Follow Up: Median 5.6 years
Mean Patient Age: Mean age 67.5 years
Female: 100

Patient Populations:

Age ≥55 years, ≥1 year postmenopausal, and established CHD or at increased risk for CHD

Exclusions:

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

Primary Endpoints:

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

Secondary Endpoints:

Stroke, venous thromboembolic events, all breast cancers, clinical vertebral fractures, death from coronary causes, death from cardiovascular causes, and death from any cause

Drug/Procedures Used:

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.

Principal Findings:

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).

Interpretation:

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.

References:

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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