Mack Wendy J, Dhungana Bala, Dowsett Sherie A, Keech Cheryl A, Feng Mei, Li Yanjie, Hodis Howard N
Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
J Womens Health (Larchmt). 2007 Apr;16(3):370-8. doi: 10.1089/jwh.2006.0014.
Raloxifene, a selective estrogen receptor modulator (SERM), decreases total and low-density lipoprotein cholesterol (LDL-C) in postmenopausal women and inhibits increases in intima-media thickness (IMT) in animal models. We tested whether up to 8 years exposure to raloxifene had an effect on subclinical atherosclerosis in the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial and the follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial.
A subsample of postmenopausal women with osteoporosis, who had completed the MORE and CORE trials and were on average 68 years of age and 19 years postmenopausal at randomization into MORE, participated in this substudy. Within 6 months of cessation of study drug in CORE, right common carotid artery IMT (CIMT) and carotid artery stiffness and arterial compliance were measured at one of two sites (San Diego and San Francisco) using high-resolution B-mode ultrasound. CIMT and arterial stiffness measures were compared between women who had received raloxifene vs. placebo; the primary analysis included only women who were >or=80% drug compliant and had used <or=6 months of lipid-lowering medication during CORE.
For the primary analysis dataset (n = 89), there was no significant difference in mean CIMT between the raloxifene and placebo groups (0.83 and 0.81 mm, respectively, p = 0.62). Carotid artery stiffness and compliance were not significantly different between treatment groups (p = 0.33 and 0.59, respectively).
These preliminary data suggest that in this self-selected group of elderly post-menopausal women with osteoporosis who were evaluated within 6 months of cessation of study medication, there were no differences between long-term raloxifene treatment and placebo groups in several measures of subclinical atherosclerosis.
雷洛昔芬是一种选择性雌激素受体调节剂(SERM),可降低绝经后女性的总胆固醇和低密度脂蛋白胆固醇(LDL-C),并在动物模型中抑制内膜中层厚度(IMT)增加。我们在雷洛昔芬评估的4年多结局(MORE)试验及后续的4年依维斯塔持续相关结局(CORE)试验中,检测了长达8年的雷洛昔芬暴露对亚临床动脉粥样硬化是否有影响。
完成MORE和CORE试验且平均年龄68岁、随机分组进入MORE时绝经19年的骨质疏松绝经后女性亚组参与了本亚研究。在CORE试验中停止研究药物治疗的6个月内,在两个地点(圣地亚哥和旧金山)之一,使用高分辨率B型超声测量右侧颈总动脉IMT、颈动脉僵硬度和动脉顺应性。比较接受雷洛昔芬与安慰剂治疗女性之间的IMT和动脉僵硬度测量值;主要分析仅纳入CORE试验中药物依从性≥80%且降脂药物使用时间≤6个月的女性。
对于主要分析数据集(n = 89),雷洛昔芬组与安慰剂组的平均IMT无显著差异(分别为0.83和0.81 mm,p = 0.62)。治疗组之间的颈动脉僵硬度和顺应性无显著差异(p分别为0.33和0.59)。
这些初步数据表明,在这个自行选择的、研究药物停止治疗6个月内接受评估的老年绝经后骨质疏松女性群体中,长期雷洛昔芬治疗组与安慰剂组在亚临床动脉粥样硬化的多项测量指标上无差异。