Clinical Question: What is the effect of raloxifene (Evista) on the risks of cardiovascular disease and breast cancer?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Previous studies have shown that raloxifene appears to reduce the risk of breast cancer and also may have beneficial cardiovascular effects. In the Raloxifene Use for The Heart (RUTH) trial, 10,101 postmenopausal women 55 years or older with known cardiovascular disease (or at high risk for it) were randomly assigned to raloxifene 60 mg per day or placebo. Patients with recent myocardial infarction, bypass surgery, or percutaneous coronary intervention were excluded, as were women who had a history of cancer or venous thromboembolism, recent unexplained uterine bleeding, heart failure, liver or renal disease, or who had recently used estrogen or other sex hormones.

The mean age of participants was 67 years, 84 percent were white, 10 percent had a family history of breast cancer, and approximately 40 percent had a five-year risk of breast cancer greater than 1.66 percent (the usual cutoff for considering prophylactic therapy). Approximately one half had a history of coronary artery disease, and 45 percent had diabetes. Groups were balanced at the start of the study except for a statistically significant difference in the cardiovascular risk score (7.9 in the raloxifene group versus 7.8 in the placebo group); however, it is unlikely that this small difference was clinically meaningful. Women were monitored for a mean of 5.6 years, and each outcome was confirmed by a committee blinded to treatment assignment.

There was no difference between groups in the risk of cardiovascular events, death from coronary disease, or nonfatal myocardial infarction. Among women taking raloxifene there was a trend toward more strokes (0.95 versus 0.86 percent per year;P = .07) and a greater risk of venous thromboembolism (0.39 versus 0.27 percent per year;P = .02; number needed to harm = 833 per year). However, the risk of invasive breast cancer was lower in the raloxifene group (0.15 versus 0.27 percent per year;P = .003; number needed to treat [NNT] = 833 per year), as was the risk of clinical vertebral fracture (0.24 versus 0.37 percent per year;P = .007; NNT = 769). There was no difference in the risk of clinical nonvertebral fracture or all-cause mortality.

Bottom Line: For every 1,000 women who take raloxifene for five years, four or five additional strokes, six additional episodes of venous thromboembolism, six fewer invasive breast cancers, and six or seven fewer clinical vertebral fractures can be expected. The cost for this treatment would be approximately $1,000 per woman per year, for a total cost of $5,000,000 at current drug prices. (Level of evidence: 1b)