Raloxifene is a selective estrogen-receptor modulator (SERM), with differential effects on various organ systems. The RUTH trial was designed to evaluate the effect of raloxifene on coronary heart disease (CHD) events and invasive breast cancer.
A total of 10101 postmenopausal women (mean age 68 years) with CHD or multiple CHD risk factors were randomized to raloxifene 60 mg/d or placebo and followed for a median of 5.6 years.
The two primary outcomes of RUTH were coronary events (first occurrence of CHD death, myocardial infarction, or hospitalized acute coronary syndrome) and invasive breast cancer.
Results
Raloxifene had no effect on coronary events overall. There was no evidence of early CHD harm, as has been shown in clinical trials of menopausal hormone therapy. Raloxifene reduced the risk of invasive breast cancer (absolute risk reduction (ARR) of 1.2 invasive breast cancers per 1000 woman-years). There was no difference between treatment groups in the incidence of all strokes or total mortality.
However, raloxifene increased the incidence of fatal stroke (absolute risk increase (ARI) 0.7 per 1000 woman-years) and lowered the incidence of non-cardiovascular deaths (ARR, 0.2 per 1000 woman-years); no specific disease category explained the decrease in non-cardiovascular death. Raloxifene increased risk of venous thromboembolism (ARI, 1.2 per 1000 woman-years) and reduced the risk of clinical vertebral fractures (ARR, 1.3 per 1000 woman-years).