McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA.
Am J Cardiol. 2010 Mar 1;105(5):656-63. doi: 10.1016/j.amjcard.2009.10.029. Epub 2009 Dec 24.
Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients > or = 65 years of age. The percentage of change from baseline in low-density lipoprotein (LDL) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease. After stabilization of atorvastatin 10-mg therapy, 1,053 patients, > or = 65 years old, at high risk of coronary heart disease, with and without atherosclerotic vascular disease and a LDL cholesterol level that was not <70 or <100 mg/dl, respectively, were randomized to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks. Ezetimibe added to atorvastatin 10 mg resulted in significantly greater changes at week 6 in LDL cholesterol (p <0.001), significantly more patients with atherosclerotic vascular disease achieving a LDL cholesterol level of <70 mg/dl (p <0.001), and significantly more patients without atherosclerotic vascular disease achieving a LDL cholesterol level of <100 mg/dl (p <0.001) at weeks 6 and 12 compared to atorvastatin 20 mg or atorvastatin 40 mg. In addition, ezetimibe plus atorvastatin 10 mg resulted in significantly greater changes at week 6 in total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B (all p <0.001), and HDL cholesterol (p = 0.021) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol, non-HDL cholesterol, apolipoprotein A-I (p = 0.001), total cholesterol, apolipoprotein B (p <0.030), and HDL cholesterol (p <0.001) compared with atorvastatin 40 mg. Both treatments were generally well tolerated, with comparable safety profiles. In conclusion, adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or =65 years old at high risk for coronary heart disease.
很少有临床研究关注降脂治疗在年龄≥65 岁患者中的疗效。本研究评估了在患有高脂血症和冠心病高危因素的年龄≥65 岁患者中，依折麦布 10mg 联合阿托伐他汀与阿托伐他汀逐步加量相比，12 周时低密度脂蛋白（LDL）胆固醇的从基线变化百分率和达到预先设定 LDL 胆固醇水平的患者比例。在阿托伐他汀 10mg 治疗稳定后，1053 名年龄≥65 岁、冠心病高危因素、有或无动脉粥样硬化性血管疾病以及 LDL 胆固醇水平分别＜70mg/dl 或＜100mg/dl 的患者被随机分配接受依折麦布联合阿托伐他汀 10mg 治疗 12 周或阿托伐他汀 20mg 治疗 6 周，随后增至阿托伐他汀 40mg 再治疗 6 周。依折麦布联合阿托伐他汀 10mg 治疗第 6 周时 LDL 胆固醇的变化显著更大（p＜0.001），有动脉粥样硬化性血管疾病的患者中 LDL 胆固醇水平达到＜70mg/dl 的比例显著更高（p＜0.001），无动脉粥样硬化性血管疾病的患者中 LDL 胆固醇水平达到＜100mg/dl 的比例显著更高（p＜0.001），而阿托伐他汀 20mg 或阿托伐他汀 40mg 组在第 6 和 12 周时无显著变化。此外，依折麦布联合阿托伐他汀 10mg 治疗第 6 周时总胆固醇、甘油三酯、非高密度脂蛋白（HDL）胆固醇、载脂蛋白 B（均 p＜0.001）和 HDL 胆固醇（p=0.021）的变化显著大于阿托伐他汀 20mg 组，第 12 周时 LDL 胆固醇、非 HDL 胆固醇、载脂蛋白 A-I（p=0.001）、总胆固醇、载脂蛋白 B（p＜0.030）和 HDL 胆固醇（p＜0.001）的变化显著大于阿托伐他汀 40mg 组。两种治疗方案总体上耐受性良好，安全性相当。总之，与阿托伐他汀 10mg 加倍或增至 4 倍剂量相比，依折麦布联合阿托伐他汀 10mg 可显著改善年龄≥65 岁、冠心病高危因素患者的大多数血脂指标，并且在 6 周和 12 周时更能达到预先设定的 LDL 胆固醇水平。
