Knopp Robert H, Retzlaff Barbara M, Fish Brian, Dowdy Alice, Twaddell Barbara, Nguyen Thuy, Paramsothy Pathmaja
Northwest Lipid Research Clinic, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington.
J Clin Lipidol. 2009;3(3):167-178. doi: 10.1016/j.jacl.2009.04.052.
The combination of niacin and statin has proven value in hyperlipidemia management and heart disease prevention. However, the efficacy of the non-prescription time-release niacin, Slo-Niacin®, is little studied alone and not at all with atorvastatin. We gave Slo-Niacin® and atorvastatin, singly and together to determine efficacy on the combined abnormalities of triglyceride, LDL and HDL. METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or 55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or incremental doses of Slo-Niacin® to 1500 mg/day. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence. RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin® decreased median triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I 5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin® treatment alone compared to atorvastatin and also decreased when Slo-Niacin® was added to atorvastatin. Six subjects dropped out, 3 for niacin related symptoms. CONCLUSIONS: Slo-Niacin® 1.5g/day with atorvastatin 10 mg/day improved lipoprotein lipids, apoproteins and inflammation markers without hepatotoxicity. Slo-Niacin® deserves further study as a cost-effective treatment of hyperlipidemia.
烟酸与他汀类药物联合使用在高脂血症管理和心脏病预防方面已被证明具有价值。然而，非处方缓释烟酸Slo-Niacin®单独使用的疗效研究较少，与阿托伐他汀联合使用的研究则完全没有。我们单独及联合给予Slo-Niacin®和阿托伐他汀，以确定其对甘油三酯、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）联合异常的疗效。
42名低密度脂蛋白胆固醇（LDL-C）>130mg/dL、高密度脂蛋白胆固醇（HDL-C）<45（男性）或<55mg/dL（女性）的男性和女性被随机分为两组，一组每天服用10mg阿托伐他汀，持续3个月，另一组服用递增剂量的Slo-Niacin®直至每日1500mg。在接下来的3个月阶段添加另一种药物。每月测量血脂谱和转氨酶，并在基线和每个治疗阶段结束时进行其他测量。
平均入组时血脂（mg/dL）为：甘油三酯（TG）187、LDL-C 171、HDL-C 39。平均体重指数（BMI）为32.6 Kg/m²。单独使用Slo-Niacin®进行单药治疗可使甘油三酯中位数降低15%，平均LDL-C降低12%，非HDL-C降低15%，HDL-C升高8%。阿托伐他汀可使甘油三酯中位数降低26%，平均LDL-C降低36%，非HDL-C降低36%，HDL-C升高6%。联合治疗可使甘油三酯中位数降低33%，平均LDL-C和非HDL-C均降低43%。HDL-C升高10%（所有p<0.001）。残余样脂蛋白-C中位数降低55%，载脂蛋白B（apo-B）平均降低40%，高敏C反应蛋白（hsCRP）中位数降低23%（所有p<0.05），肿瘤坏死因子α（TNFα）降低12%，白细胞介素-6（IL-6）无变化。平均LDL浮力增加15%，载脂蛋白A-I（apo-A-I）增加5%，HDL2-C中位数增加20%（所有p<0.05）。与阿托伐他汀相比，单独使用Slo-Niacin®治疗时丙氨酸转氨酶（ALT）下降，当Slo-Niacin®与阿托伐他汀联合使用时ALT也降低。6名受试者退出研究，3名因烟酸相关症状退出。
每天1.5g的Slo-Niacin®与10mg阿托伐他汀联合使用可改善脂蛋白血脂、载脂蛋白和炎症标志物，且无肝毒性。Slo-Niacin®作为一种具有成本效益的高脂血症治疗药物值得进一步研究。
