Bays Harold, Rhyne James, Abby Stacey, Lai Yu-Ling, Jones Michael
Louisville Metabolic and Atherosclerosis Research Center Inc., Louisville, KY 40213, USA.
Curr Med Res Opin. 2006 Nov;22(11):2191-200. doi: 10.1185/030079906X148436.
The primary aim of this study was to compare the effect of colesevelam HCl in combination with ezetimibe to ezetimibe monotherapy on low-density lipoprotein cholesterol (LDL-C) levels in subjects with primary hypercholesterolemia.
Subjects with primary hypercholesterolemia (N = 86) were enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a 4- to 8-week washout period, subjects received colesevelam HCl 3.8 g/day plus ezetimibe 10 mg/day or colesevelam HCl placebo plus ezetimibe 10 mg/day for 6 weeks. The primary efficacy endpoint was the mean percent change in LDL-C during randomized treatment. Secondary endpoints included mean absolute change in LDL-C, mean absolute and mean percent change in levels of high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), apolipoprotein (apo) A-I and apo B, and median absolute and percent changes in triglycerides (TG) and high-sensitivity C-reactive protein from baseline to end of treatment. Of the 86 subjects randomized to treatment, 85 were included in the intent-to-treat analysis.
After 6 weeks of treatment, colesevelam HCl plus ezetimibe produced a mean percent change in LDL-C of -32.3% versus -21.4% with ezetimibe monotherapy (p < 0.0001). Colesevelam HCl plus ezetimibe was significantly more effective than ezetimibe alone at producing mean percent reductions in TC, non-HDL-C, and apo B and increases in apo A-I (p < 0.005 for all). Neither treatment regimen resulted in significant changes in median TG levels compared with baseline (p = NS). Both treatments were safe and generally well tolerated.
Colesevelam HCl plus ezetimibe combination therapy significantly reduced mean LDL-C, TC, non-HDL-C, and apo B levels and increased apo A-I levels (p < 0.005 for all) without significantly increasing median TG levels in hypercholesterolemic subjects compared with ezetimibe alone. Although limited in that atherosclerotic coronary heart disease outcomes were not evaluated, this study demonstrated that combining colesevelam HCl with ezetimibe is a therapeutic option in hypercholesterolemic patients, such as those in whom statins are contraindicated and/or who may have intolerances to statin therapy.
本研究的主要目的是比较盐酸考来维仑联合依折麦布与依折麦布单药治疗对原发性高胆固醇血症患者低密度脂蛋白胆固醇（LDL-C）水平的影响。
原发性高胆固醇血症患者（N = 86）被纳入一项多中心、随机、双盲、安慰剂对照、平行组研究。经过4至8周的洗脱期后，患者接受3.8克/天的盐酸考来维仑加10毫克/天的依折麦布或盐酸考来维仑安慰剂加10毫克/天的依折麦布治疗6周。主要疗效终点是随机治疗期间LDL-C的平均变化百分比。次要终点包括LDL-C的平均绝对变化、高密度脂蛋白胆固醇（HDL-C）、非HDL-C、总胆固醇（TC）、载脂蛋白（apo）A-I和apo B水平的平均绝对变化和平均变化百分比，以及从基线到治疗结束时甘油三酯（TG）和高敏C反应蛋白的中位数绝对变化和百分比变化。在随机接受治疗的86名受试者中，85名被纳入意向性分析。
治疗6周后，盐酸考来维仑加依折麦布使LDL-C的平均变化百分比为-32.3%，而依折麦布单药治疗为-21.4%（p < 0.0001）。盐酸考来维仑加依折麦布在使TC、非HDL-C和apo B的平均百分比降低以及apo A-I升高方面比单独使用依折麦布显著更有效（所有p < 0.005）。与基线相比，两种治疗方案均未导致TG中位数水平有显著变化（p =无统计学意义）。两种治疗均安全且一般耐受性良好。
与单独使用依折麦布相比，盐酸考来维仑加依折麦布联合治疗显著降低了高胆固醇血症患者的平均LDL-C、TC、非HDL-C和apo B水平，并提高了apo A-I水平（所有p < 0.005），且未显著增加TG中位数水平。尽管本研究存在局限性，即未评估动脉粥样硬化性冠心病结局，但该研究表明，将盐酸考来维仑与依折麦布联合使用是高胆固醇血症患者的一种治疗选择，例如那些他汀类药物禁忌和/或可能对他汀类治疗不耐受的患者。
