Barrett-Connor E et al. (2006) Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355: 125–137

In 1998, the Raloxifene Use for The Heart study was launched to investigate whether the selective estrogen-receptor modulator raloxifene reduces the risk of clinical coronary events and/or invasive breast cancer.

This randomized, double-blind trial recruited 10,001 postmenopausal women (mean age 67.5 years) with established coronary heart disease (CHD) or multiple CHD risk factors. Of these women, 5,044 were randomly allocated to receive 60 mg raloxifene daily; the rest received placebo. The incidence of invasive breast cancer and coronary events (including death from coronary causes, hospitalization for an acute coronary syndrome, and nonfatal myocardial infarction) was recorded over a median follow-up of 5.56 years.

Raloxifene treatment approximately halved the risk of invasive breast cancer (absolute risk reduction 1.2 cases per 1,000 women treated for 1 year), and was associated with a 33% lower incidence of all breast cancer, compared with placebo. Markedly fewer clinical vertebral fractures occurred in patients given raloxifene than in controls. Raloxifene treatment did not affect the risk of primary coronary events, but treated patients were nearly 1.5 times more likely to suffer venous thromboembolism or fatal stroke than controls. Hot flashes, leg cramps, and peripheral edema were also associated with raloxifene treatment.

The authors conclude that, although raloxifene treatment reduces the risk of invasive breast cancer, it does not reduce risk of coronary events in postmenopausal women with, or at increased risk for, CHD. Patients and clinicians must consider both the benefits and risks of raloxifene when contemplating its use.