Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2009.01.033 Byline: Elizabeth Barrett-Connor (a), David A. Cox (b), Jingli Song (b), Bruce Mitlak (b), Lori Mosca (c), Deborah Grady (d) Keywords: Framingham; Raloxifene; SERM; Stroke Abstract: 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. Author Affiliation: (a) Departments of Family and Preventive Medicine, University of California, San Diego, La Jolla, Calif (b) Lilly Research Laboratories, Indianapolis, Ind (c) Preventive Cardiology, Columbia University Medical Center, New York, NY (d) University of California, San Francisco and the San Francisco VA Medical Center, Calif Article Note: (footnote) 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.

Background: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women. Methods: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. Results: Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change [+ or -] SE), -1.32% [+ or -] 0.22%; raloxifene, 30 mg, 0.71% [+ or -] 0.23%; raloxifene, 60 mg, 1.28% [+ or -] 0.23%; and raloxifene, 150 mg, 1.20% [+ or -] 0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). Conclusions: Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450