Raloxifene decreases breast CA risk, no effect on CVD risk (RUTH)

Clinical Question

What is the effect of raloxifene on the risks of cardiovascular disease and breast cancer?

Bottom Line

For every 1000 women who take raloxifene for 5 years, we can expect 4 to 5 additional strokes, 6 additional episodes of venous thromboembolism (VTE), 6 fewer invasive breast cancers, and 6 to 7 fewer clinical vertebral fractures. The cost for this mixed bag of benefits and harms would be approximately $1000 per woman per year, for a total cost of $5,000,000 at current drug prices. (LOE = 1b)


Barrett-Connor E, Mosca L, Collins P, et al, for the Raloxifene Use for The Heart (RUTH) Trial Investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006;355:125-137.  [PMID:16837676]

Study Design

Randomized controlled trial (double-blinded)






Outpatient (any)


Previous studies have shown that raloxifene appears to reduce the risk of breast cancer and may also have beneficial cardiovascular effects. In the current 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 VTE, 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% were white, 10% had a family history of breast cancer, and approximately 40% had a 5-year risk of breast cancer greater than 1.66% (the usual cutoff for considering prophylactic therapy). Approximately half had a history of coronary artery disease and 45% were diabetic. 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 vs 7.8 in the placebo group). However, it is unlikely that this small difference was clinically meaningful. Women were followed up for a mean of 5.6 years, and outcomes were adjudicated by a committee blinded to treatment assigned. There was no difference between groups in the risk of "all bad cardiovascular things," death from coronary disease, or nonfatal myocardial infarction. Among women taking raloxifene, there was a trend toward more strokes (0.95% vs 0.86% per year; P = .07) and a greater risk of VTE (0.39% vs 0.27% per year; P = .02; number needed to treat to harm = 833/year). However, the risk of invasive breast cancer was lower in the raloxifene group (0.15% vs 0.27% per year; P = .003; number needed to treat [NNT] = 833/year), as was the risk of clinical vertebral fracture (0.24% vs 0.37% per year; P = .007; NNT = 769). There was no difference in the risk of clinical nonvertebral fracture or all-cause mortality.