Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women

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.