Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.
BACKGROUND
The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established.


METHODS
We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer.


RESULTS
As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000).


CONCLUSIONS
Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593 [ClinicalTrials.gov].).
Barrett-Connor
Elizabeth
E
Department of Family and Preventive Medicine, University of California, San Diego, La Jolla 92093-0607, USA. ebarrettconnor@ucsd.edu
Mosca
Lori
L
Collins
Peter
P
Geiger
Mary Jane
MJ
Grady
Deborah
D
Kornitzer
Marcel
M
McNabb
Michelle A
MA
Wenger
Nanette K
NK
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology*; D003327:Coronary Disease / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D016103:Spinal Fractures / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology; D013923:Thromboembolism / Q000453:epidemiology
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride