Bays Harold E, Dujovne Carlos A, McGovern Mark E, White T Eric, Kashyap Moti L, Hutcheson A Gene, Crouse John R
Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky 40213, USA.
Am J Cardiol. 2003 Mar 15;91(6):667-72. doi: 10.1016/s0002-9149(03)00007-9.
This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels > or =160 mg/dl without coronary artery disease, or > or =130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a).
本研究比较了每日一次的烟酸缓释（ER）/洛伐他汀固定剂量组合与标准剂量阿托伐他汀或辛伐他汀的相对疗效，特别强调了相对起始剂量。低密度脂蛋白（LDL）胆固醇升高且高密度脂蛋白（HDL）胆固醇血液水平降低的受试者（n = 315）（定义为无冠状动脉疾病时LDL胆固醇血液水平≥160mg/dl，或存在冠状动脉疾病时≥130mg/dl，男性HDL胆固醇<45mg/dl，女性<50mg/dl）被随机分配至阿托伐他汀、辛伐他汀或烟酸ER/洛伐他汀组，治疗16周。主要疗效变量为LDL胆固醇和HDL胆固醇水平相对于基线的平均变化百分比。8周后，起始剂量为1000/40mg的烟酸ER/洛伐他汀和10mg起始剂量的阿托伐他汀均使平均LDL胆固醇降低了38%。12周后，1000/40mg的烟酸ER/洛伐他汀使LDL胆固醇降低了42%，而20mg起始剂量的辛伐他汀使LDL胆固醇降低了34%（p<0.001）。在所有比较剂量下，烟酸ER/洛伐他汀升高HDL胆固醇的幅度均显著大于阿托伐他汀或辛伐他汀（p<0.001）。烟酸ER/洛伐他汀还使甘油三酯、脂蛋白（a）、载脂蛋白A-1、载脂蛋白B和HDL亚组分有显著改善。共有6%接受烟酸ER/洛伐他汀治疗的研究受试者因潮红而退出。各研究组因肝酶升高导致停药的情况无显著差异。未观察到药物性肌病。在降低LDL胆固醇方面，烟酸ER/洛伐他汀与10mg阿托伐他汀相当，且比20mg辛伐他汀更有效；在升高HDL胆固醇方面，烟酸ER/洛伐他汀比阿托伐他汀或辛伐他汀更有效，并且在非HDL胆固醇、甘油三酯和脂蛋白（a）方面提供了更大的整体改善。
