Derosa Giuseppe, D'Angelo A, Franzetti I G, Ragonesi P D, Gadaleta G, Scalise F, Ciccarelli L, Piccinni M N, Cicero A F G
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
J Clin Pharm Ther. 2009 Jun;34(3):267-76. doi: 10.1111/j.1365-2710.2008.01004.x.
One of the problems associated with reaching the low-density lipoprotein cholesterol (LDL-C) target during statin treatment is the emergence of laboratory or clinical side effects. The aim of our study was to evaluate the prevalence of statin-associated adverse events in diabetic and non-diabetic patients affected by polygenic hypercholesterolemia or combined hyperlipidemia and the efficacy and tolerability of treatment with ezetimibe/simvastatin 10/10 mg/day on the same subjects experiencing the adverse events.
Consecutively enrollment of patients affected by polygenic hypercholesterolemia or combined hyperlipidemia with or without type 2 diabetes mellitus. Each Centre used any of the available statins on the basis of current clinical judgement and monitored enrolled patients for adverse events during the following 2 years. Those patients with moderate adverse events suspended the current statin therapy for 1 month (washout period), and then were shifted to treatment with ezetimibe/simvastatin 10/10 mg/day and again monitored for adverse events in the following 6 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine phosphokinase and monitored adverse events such as asthenia and myalgia.
All 1170 Caucasian patients affected by polygenic hypercholesterolemia obtained a significant reduction in LDL-C during the observation period (P < 005), while those with combined hyperlipidemia also showed a reduction in TG plasma level (P < 005) and a significant increase in HDL-C (P < 005). Patients affected by polygenic hypercholesterolemia experiencing adverse event under statin treatment obtained a significantly lower reduction than those tolerating the treatment (P < 0001). The prevalence of adverse events under statin treatment was 49% in non-diabetic patients with polygenic hypercholesterolemia, 86% in those with combined hyperlipidemia, 71% in diabetic patients with polygenic hypercholesterolemia and 76% in those with combined hyperlipidemia. Six months after the shift to treatment with ezetimibe/simvastatin 10/10 mg, all patients experienced a significant improvement in LDL-C, TG and HDL-C plasma level. No adverse event was registered during the ezetimibe/simvastatin 10/10 mg treatment period. It seems that previous side effects observed with statins did not re-appear with the administration of ezetimibe/simvastatin 10/10 mg/day.
The efficacy and adverse effect profile of the ezetimibe and simvastatin combination appear to be good for both diabetic and nondiabetic patients, and in both conditions.
他汀类药物治疗期间，实现低密度脂蛋白胆固醇（LDL-C）目标所面临的问题之一是出现实验室或临床副作用。我们研究的目的是评估受多基因高胆固醇血症或混合性高脂血症影响的糖尿病和非糖尿病患者中他汀类药物相关不良事件的发生率，以及依折麦布/辛伐他汀10/10毫克/天对出现不良事件的同一受试者的治疗效果和耐受性。
连续纳入受多基因高胆固醇血症或混合性高脂血症影响、有或无2型糖尿病的患者。各中心根据当前临床判断使用任何一种可用的他汀类药物，并在接下来的2年中监测入组患者的不良事件。那些出现中度不良事件的患者暂停当前他汀类药物治疗1个月（洗脱期），然后改用依折麦布/辛伐他汀10/10毫克/天治疗，并在接下来的6个月中再次监测不良事件。我们评估了体重指数、糖化血红蛋白、空腹血糖、总胆固醇、LDL-C、高密度脂蛋白胆固醇、甘油三酯、丙氨酸转氨酶、天冬氨酸转氨酶、肌酸磷酸激酶，并监测了诸如乏力和肌痛等不良事件。
所有1170例受多基因高胆固醇血症影响的白种人患者在观察期内LDL-C均显著降低（P<0.05），而混合性高脂血症患者的血浆甘油三酯水平也有所降低（P<0.05），HDL-C显著升高（P<0.05）。在他汀类药物治疗下出现不良事件的多基因高胆固醇血症患者，其LDL-C降低幅度明显低于耐受治疗的患者（P<0.001）。他汀类药物治疗下不良事件的发生率在多基因高胆固醇血症的非糖尿病患者中为4.9%，混合性高脂血症患者中为8.6%，多基因高胆固醇血症的糖尿病患者中为7.1%，混合性高脂血症患者中为7.6%。改用依折麦布/辛伐他汀10/10毫克治疗6个月后，所有患者的LDL-C、甘油三酯和HDL-C血浆水平均有显著改善。在依折麦布/辛伐他汀10/10毫克治疗期间未记录到不良事件。似乎之前用他汀类药物观察到的副作用在使用依折麦布/辛伐他汀10/10毫克/天时未再次出现。
依折麦布与辛伐他汀联合使用的疗效和不良反应情况，对于糖尿病和非糖尿病患者以及这两种情况下似乎都较好。
