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

JAMA. 1998 May 13;279(18):1445-51. doi: 10.1001/jama.279.18.1445.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Blood Coagulation Factors / metabolism*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Double-Blind Method
  • Estrogen Antagonists / pharmacology*
  • Estrogen Replacement Therapy* / adverse effects
  • Estrogens / agonists*
  • Estrogens, Conjugated (USP) / pharmacology
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Humans
  • Lipoproteins / blood*
  • Medroxyprogesterone Acetate / therapeutic use
  • Middle Aged
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use*
  • Postmenopause
  • Progesterone Congeners / therapeutic use
  • Prospective Studies
  • Raloxifene Hydrochloride
  • Risk Factors

Substances

  • Blood Coagulation Factors
  • Estrogen Antagonists
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Lipoproteins
  • Piperidines
  • Progesterone Congeners
  • Raloxifene Hydrochloride
  • Medroxyprogesterone Acetate