Division of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama City, Kanagawa 232-0024, Japan.
Atherosclerosis. 2012 Oct;224(2):454-6. doi: 10.1016/j.atherosclerosis.2012.07.036. Epub 2012 Aug 4.
To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin.
Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks.
Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks.
Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.
评估依折麦布联合他汀类药物降低 LDL-C 的长期作用机制。
将 LDL-C≥70mg/dL 的经阿托伐他汀 10mg/天或瑞舒伐他汀 2.5mg/天治疗的冠心病患者随机分为依折麦布 10mg/天+他汀（n=78）或他汀加倍（n=72）组，治疗 52 周。
依折麦布联合他汀组 LDL-C 降低幅度更大且持续至 52 周，而他汀加倍组 LDL-C 水平在 12 周后再次升高。尽管植物固醇/TC 增加，但依折麦布联合他汀组胆固醇甾醇/TC 下降更明显。相反，他汀加倍组植物固醇/TC 不变而胆固醇甾醇/TC 增加，使胆固醇甾醇/植物固醇比值在 52 周内增加。与依折麦布联合他汀组相比，他汀加倍组在 12 周时血浆 PCSK9 水平更高，但在 52 周时相似。
尽管两组之间 PCSK9 的差异是短暂的，但胆固醇甾醇和植物固醇的差异持续到 52 周。这些结果表明，胆固醇吸收和合成的同时抑制可使 LDL-C 水平稳定且更大幅度降低。
