Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.
In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.
Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).
In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”
“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).
The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).
A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.
A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.
The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.
Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.
In both groups, the mean age was 68 years.
There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).
Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.
The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.
The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”
There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.
The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.
The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.
However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.
Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.
The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.
In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.