Raloxifene and Risk for Stroke Based on the Framingham Stroke Risk Score
published online 19 June 2009.
Abstract
Purpose
Raloxifene reduces vertebral fracture and invasive breast cancer risks, but increases fatal strokes in postmenopausal women at increased coronary risk. We assessed whether this risk is concentrated in postmenopausal women already at high stroke risk.
Methods
Raloxifene Use for The Heart (RUTH) enrolled 10,101 postmenopausal women (mean age 67 years) with or at increased coronary heart disease risk; Multiple Outcomes of Raloxifene Evaluation (MORE) enrolled 7705 osteoporotic postmenopausal women (mean age 66 years). A Framingham Stroke Risk Score (FSRS) was calculated for all women with no prior cerebrovascular events (n=16,858). The validity of the FSRS was assessed in the placebo groups, and then raloxifene-associated stroke risk was analyzed by FSRS subgroups.
Results
FSRS predicted an increased stroke risk in the placebo group of both clinical trials. There was no difference in the incidence of nonfatal strokes between the raloxifene and placebo groups in MORE or RUTH, regardless of baseline Framingham stroke risk. In RUTH, women with FSRS <13 showed no increase in raloxifene-associated fatal stroke risk (hazard ratio [HR] 1.08; 95% confidence interval [CI], 0.49-2.37). Those with FSRS ≥13 had a 75% increased risk of raloxifene-associated fatal stroke (HR 1.75; 95% CI, 1.01-3.02; interaction P=.33). In MORE, where 80% of women had a FSRS <13, no increase in fatal (HR 0.57; 95% CI, 0.19-1.68) stroke risk was observed.
Discussion
Risk of fatal stroke associated with raloxifene was greater in women at high stroke risk. These results might be useful for identifying postmenopausal women at high risk of first stroke who should avoid raloxifene therapy.
cPreventive Cardiology, Columbia University Medical Center, New York, NY
dUniversity of California, San Francisco and the San Francisco VA Medical Center, Calif
Requests for reprints should be addressed to Elizabeth Barrett-Connor, MD, Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, 9500 Gilman Drive 0607, La Jolla, CA 92093-0607
Funding: Studies funded by Lilly Research Laboratories.
Conflict of Interest: Elizabeth Barrett-Connor and Deborah Grady were paid external investigators for the Raloxifene MORE and RUTH studies by Lilly Research Laboratories. Lori Mosca was a paid external investigator for the Raloxifene RUTH study by Lilly Research Laboratories. David A. Cox, Jingli Song, and Bruce Mitlak are employees of Lilly Research Laboratories and have financial interest in the company.
Authorship: All authors had access to the data and a role in writing the manuscript.
ABSTRACT
