Insull William, Davidson Michael H, Kulkarni Pandurang M, Siddhanti Suresh, Ciaccia Angelina V, Keech Cheryl A
Lipid Research Clinic, Baylor College of Medicine and the Methodist Hospital, Houston, TX 77030-2711, USA.
Metabolism. 2005 Jul;54(7):939-46. doi: 10.1016/j.metabol.2005.02.010.
Abstract Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d. Raloxifene, simvastatin, and coadministration therapy reduced mean LDL cholesterol by 10.5%, 23.3%, and 31.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo), and mean apolipoprotein B by 10.4%, 24.2%, and 30.0% from baseline, respectively ( P < .003 vs baseline; P < .02 vs placebo). Each active treatment decreased non-HDL cholesterol compared with placebo ( P < .01). Coadministration treatment was more effective than either monotherapy in reducing LDL cholesterol ( P < .05). Coadministration treatment reduced mean apolipoprotein B ( P < .001) and non-HDL cholesterol ( P < .001) when compared with raloxifene, but was not significantly different when compared with simvastatin. Coadministration therapy increased HDL cholesterol and apolipoprotein A1 levels compared with placebo ( P < .02). No significant effect on triglycerides, very low density lipoprotein cholesterol, and lipoprotein (a) occurred with any active treatment. Raloxifene, simvastatin, and the coadministration therapy were generally well tolerated with clinical adverse effects similar to placebo. No woman had clinically significant elevated liver function tests requiring drug discontinuation. Further data on safety and lipid-lowering effects are needed before raloxifene and statin coadministration may be considered as therapeutic interventions for treating postmenopausal women to achieve National Cholesterol Education Program-Adult Treatment Panel III treatment guidelines.
雷洛昔芬和低剂量辛伐他汀均可降低低密度脂蛋白（LDL）胆固醇，而不影响高密度脂蛋白（HDL）胆固醇和甘油三酯。这项为期12周的双盲研究的目的是确定雷洛昔芬和辛伐他汀联合用药在影响空腹脂蛋白和载脂蛋白方面是否比单一疗法具有额外益处。95名绝经后女性，其LDL胆固醇中度升高（平均146mg/dL），被随机分为安慰剂组、雷洛昔芬60mg/d组、辛伐他汀10mg/d组或雷洛昔芬60mg/d与辛伐他汀10mg/d联合用药组。雷洛昔芬、辛伐他汀及联合用药治疗分别使平均LDL胆固醇较基线水平降低了10.5%、23.3%和31.0%（与基线水平相比，P<.003；与安慰剂相比，P<.02），平均载脂蛋白B较基线水平分别降低了10.4%、24.2%和30.0%（与基线水平相比，P<.003；与安慰剂相比，P<.02）。与安慰剂相比，每种活性治疗均降低了非HDL胆固醇（P<.01）。联合用药治疗在降低LDL胆固醇方面比单一疗法更有效（P<.05）。与雷洛昔芬相比，联合用药治疗降低了平均载脂蛋白B（P<.001）和非HDL胆固醇（P<.001），但与辛伐他汀相比无显著差异。与安慰剂相比，联合用药治疗增加了HDL胆固醇和载脂蛋白A1水平（P<.02）。任何活性治疗对甘油三酯、极低密度脂蛋白胆固醇和脂蛋白（a）均无显著影响。雷洛昔芬、辛伐他汀及联合用药治疗一般耐受性良好，临床不良反应与安慰剂相似。没有女性出现需要停药的具有临床意义的肝功能检查值升高。在考虑将雷洛昔芬和他汀类药物联合用药作为治疗绝经后女性以达到国家胆固醇教育计划成人治疗小组第三次报告治疗指南的治疗干预措施之前，还需要进一步的安全性和降脂效果数据。
