Walsh B W, Kuller L H, Wild R A, Paul S, Farmer M, Lawrence J B, Shah A S, Anderson P W
Brigham and Women's Hospital, Boston, Mass 02115, USA.
JAMA. 1998 May 13;279(18):1445-51. doi: 10.1001/jama.279.18.1445.
Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.
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).
Double-blind, randomized, parallel trial.
Eight sites in the United States.
390 healthy postmenopausal women recruited by advertisement.
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.
Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment.
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.
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.
雷洛昔芬是一种选择性雌激素受体调节剂，对骨骼具有雌激素激动作用，对乳腺和子宫具有雌激素拮抗作用。
确定雷洛昔芬对绝经后女性心血管风险标志物的影响，并将其与激素替代疗法（HRT）诱导的影响进行比较。
双盲、随机、平行试验。
美国的八个地点。
通过广告招募的390名健康绝经后女性。
参与者被随机分配接受4种治疗中的1种：雷洛昔芬，60毫克/天；雷洛昔芬，120毫克/天；HRT（结合马雌激素，0.625毫克/天，和醋酸甲羟孕酮，2.5毫克/天）；或安慰剂。
治疗3个月和6个月后血脂水平和凝血参数相对于基线的变化及变化百分比。
在最后一次完成的访视中，与安慰剂相比，两种剂量的雷洛昔芬均使低密度脂蛋白胆固醇（LDL-C）显著降低12%（P<.001），与HRT降低14%相似（P<.001）。两种剂量的雷洛昔芬均使脂蛋白（a）显著降低7%至8%（P<.001），低于HRT降低19%（P<.001）。雷洛昔芬使高密度脂蛋白2胆固醇（HDL2-C）升高15%至17%（P<.05），低于HRT升高33%（P<.001）。雷洛昔芬对高密度脂蛋白胆固醇（HDL-C）、甘油三酯或纤溶酶原激活物抑制剂-1（PAI-1）无显著影响；而HRT使HDL-C升高11%，甘油三酯升高20%，并使PAI-1降低29%（所有P<.001）。雷洛昔芬使纤维蛋白原显著降低12%至14%（P<.001），与HRT不同，HRT对此无影响。两种治疗均未改变纤维蛋白肽A或凝血酶原片段1和2。
雷洛昔芬通过降低LDL-C、纤维蛋白原和脂蛋白（a），以及升高HDL2-C而不升高甘油三酯，有利地改变了心血管风险的生化标志物。与HRT不同，雷洛昔芬对HDL-C和PAI-1无影响，对HDL2-C和脂蛋白（a）的影响较小。需要进一步的临床试验来确定这些有利的生化作用是否与预防心血管疾病相关。
