Bays Harold E, Davidson Michael, Jones Michael R, Abby Stacey L
Louisville Metabolic and Atherosclerosis Research Center Incorporated, Louisville, Kentucky, USA.
Am J Cardiol. 2006 Apr 15;97(8):1198-205. doi: 10.1016/j.amjcard.2005.11.039. Epub 2006 Mar 3.
Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with an increased risk of atherosclerotic coronary heart disease (CHD). The addition of the bile acid sequestrants, such as colesevelam hydrochloride (HCl), to statins further reduces low-density lipoprotein (LDL) cholesterol levels. However, the effects of approved cholesterol-lowering bile acid sequestrants on hs-CRP have not previously been reported. Three randomized, double-blind, placebo-controlled, parallel, 6-week clinical trials of similar design investigated the efficacy of adding colesevelam HCl to stable simvastatin, atorvastatin, or pravastatin treatment in 204 patients with primary hypercholesterolemia. The primary end point was the mean percent change in the LDL cholesterol levels. Secondary end points included the effects on other lipid parameters and hs-CRP levels. A pooled analysis showed that adding colesevelam HCl to statin therapy significantly lowered LDL cholesterol levels (21 mg/dl or 16% mean reduction from baseline, p = 0.0013, and 11 mg/dl or 9% mean reduction compared with placebo, p = 0.0003). Four times as many patients receiving colesevelam HCl plus a statin achieved a LDL cholesterol target of <100 mg/dl compared with patients receiving a statin plus placebo (39% vs 10%, respectively, p <0.0001). The incidence of mild gastrointestinal adverse effects was slightly higher in the colesevelam HCl plus statin group than in the placebo plus statin group. Finally, the differences in the change in hs-CRP levels with colesevelam HCl plus statin therapy were significant compared with the changes with placebo plus statin (median change -23%, p = 0.0069). In conclusion, this is the first report suggesting that an approved cholesterol-lowering bile acid sequestrant, specifically colesevelam HCl, decreases hs-CRP levels when added to statin therapy.
高敏C反应蛋白（hs-CRP）水平升高与动脉粥样硬化性冠心病（CHD）风险增加相关。在他汀类药物中添加胆汁酸螯合剂，如盐酸考来维仑（HCl），可进一步降低低密度脂蛋白（LDL）胆固醇水平。然而，此前尚未报道过已获批的降胆固醇胆汁酸螯合剂对hs-CRP的影响。三项设计相似的随机、双盲、安慰剂对照、平行、为期6周的临床试验，研究了在204例原发性高胆固醇血症患者中，在稳定的辛伐他汀、阿托伐他汀或普伐他汀治疗基础上加用盐酸考来维仑的疗效。主要终点是LDL胆固醇水平的平均变化百分比。次要终点包括对其他血脂参数和hs-CRP水平的影响。一项汇总分析表明，在他汀类药物治疗中添加盐酸考来维仑可显著降低LDL胆固醇水平（降低21mg/dl或较基线平均降低16%，p = 0.0013；与安慰剂相比降低11mg/dl或平均降低9%，p = 0.0003）。与接受他汀类药物加安慰剂的患者相比，接受盐酸考来维仑加他汀类药物的患者实现LDL胆固醇目标<100mg/dl的人数是前者的四倍（分别为39%和10%，p <0.0001）。盐酸考来维仑加他汀类药物组轻度胃肠道不良反应的发生率略高于安慰剂加他汀类药物组。最后，与安慰剂加他汀类药物相比，盐酸考来维仑加他汀类药物治疗时hs-CRP水平变化的差异具有显著性（中位变化-23%，p = 0.0069）。总之，这是首份表明已获批的降胆固醇胆汁酸螯合剂，特别是盐酸考来维仑，在添加到他汀类药物治疗中时可降低hs-CRP水平的报告。
