Divisão de Cardiologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2012 Nov;45(11):1095-101. doi: 10.1590/s0100-879x2012007500118. Epub 2012 Jul 19.
Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.
有效的他汀类药物治疗与心血管事件的显著减少有关。然而，联合降脂治疗对 LDL 胆固醇目标的充分获益的解释仍存在争议。我们的研究比较了两种同样有效的降脂策略对胆固醇合成和吸收标志物的影响。这是一项前瞻性、开放标签、随机、平行设计的研究，终点设盲，共纳入 116 例患者。我们比较了 12 周 40mg 瑞舒伐他汀或 40mg 辛伐他汀/10mg 依折麦布联合治疗对胆固醇吸收标志物（菜甾醇和β-谷甾醇）、合成标志物（去甲二氢胆固醇）及其与胆固醇比值的影响。两种治疗方法均能相似地降低总胆固醇、LDL 胆固醇、甘油三酯和载脂蛋白 B，并增加载脂蛋白 A1（与基线相比，所有 P < 0.05）。辛伐他汀/依折麦布增加了血浆去甲二氢胆固醇（P = 0.012 与基线相比），并降低了菜甾醇和β-谷甾醇（与基线相比，均 P < 0.0001），与瑞舒伐他汀相比，去甲二氢胆固醇更高（P = 0.007），而菜甾醇和β-谷甾醇更低（两者均 P < 0.0001）。此外，瑞舒伐他汀增加了这些标志物与胆固醇的比值（与基线相比，所有 P < 0.002），而辛伐他汀/依折麦布显著降低了菜甾醇/胆固醇比值（P = 0.008 与基线相比），并使去甲二氢胆固醇/胆固醇比值增加三倍（P < 0.0001 与基线相比）。接受辛伐他汀/依折麦布治疗的患者的菜甾醇/胆固醇和β-谷甾醇/胆固醇比值较低，而去甲二氢胆固醇/胆固醇比值较高（与瑞舒伐他汀相比，所有 P < 0.0001）。两种同样有效的降脂策略之间观察到胆固醇吸收和合成标志物的明显差异。
