Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women - A 2-year, placebo-controlled study

Currently raloxifene, a selective estrogen receptor modulator, is being inv estigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease. We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens (CEEs). Analyses were base d on 56 hysterectomized but otherwise healthy postmenopausal women aged 54. 8 +/- 3.5 (mean +/- SD) years who entered this double-blind study and who w ere randomly assigned to raloxifene hydrochloride 60 mg/d (n = 15) or 150 m g/d (n = 13), placebo (n = 13), or CEEs 0.625 mg/d (n= 15). At baseline and after 6, 12, and 24 months of treatment, we assessed serum lipids, blood p ressure, glucose metabolism, C-reactive protein, and various hemostatic par ameters. Compared with placebo, both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L (all P < 0.04 ) and lowered, at 24 months, the level of fibrinogen by 0.71 to 0.86 g/L (a ll P < 0.05). The effects of raloxifene and CEEs did not differ significant ly. In contrast to raloxifene, from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen act ivator inhibitor-1 antigen by 30.6 to 48.6 ng/mL (all P < 0.02 versus both placebo and raloxifene). CEEs transiently increased C-reactive protein by 1 .0 mg/L at 6 months (P < 0.05 versus placebo) and prothrombin-derived fragm ent F1 + 2 by 0.79 nmol/L at 12 months (P < 0.001 versus placebo). Finally, from 12 months on, CEEs increased triglycerides by 0.33 to 0.56 mmol/L (al l P < 0.05 versus both placebo and raloxifene), Our findings suggest that i n healthy postmenopausal women, raloxifene and estrogen monotherapy have si milar beneficial effects on low density lipoprotein cholesterol and fibrino gen levels. These treatments differ, however, in their effects on high dens ity lipoprotein cholesterol, triglycerides, and plasminogen activator inhib itor-1 and possibly in their effects on prothrombin fragment F1 + 2 and C-r eactive protein.