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Original Contribution
May 13, 1998

Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women

Author Affiliations

From the Brigham and Women's Hospital, Boston, Mass (Dr Walsh); University of Pittsburgh, Pittsburgh, Pa (Dr Kuller); University of Oklahoma Health Sciences Center, Oklahoma City (Dr Wild); Lilly Research Laboratories, Indianapolis, Ind (Drs Paul, Lawrence, Shah, and Anderson); and Clinical Studies, St Petersburg, Fla (Dr Farmer).

JAMA. 1998;279(18):1445-1451. doi:10.1001/jama.279.18.1445

Context.— Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.

Objective.— To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT).

Design.— Double-blind, randomized, parallel trial.

Setting.— Eight sites in the United States.

Participants.— 390 healthy postmenopausal women recruited by advertisement.

Intervention.— Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo.

Main Outcome Measures.— Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment.

Results.— At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P<.001), similar to the 14% reduction with HRT (P<.001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P<.001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P<.05), less than the 33% increase with HRT (P<.001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P< .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P<.001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2.

Conclusions.— Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.