Taylor Allen J, Villines Todd C, Stanek Eric J, Devine Patrick J, Griffen Len, Miller Michael, Weissman Neil J, Turco Mark
Cardiology Service, Walter Reed Army Medical Center, Washington, DC, USA.
N Engl J Med. 2009 Nov 26;361(22):2113-22. doi: 10.1056/NEJMoa0907569. Epub 2009 Nov 15.
Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level.
We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial.
The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test).
This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)
在他汀类药物单药治疗基础上加用其他治疗以进一步改善血脂谱，可采用联合治疗，目的是升高高密度脂蛋白（HDL）胆固醇水平或进一步降低低密度脂蛋白（LDL）胆固醇水平。
我们纳入了患有冠心病或冠心病风险等同疾病、正在接受长期他汀类药物治疗且LDL胆固醇水平低于100mg/分升（2.6mmol/升）、HDL胆固醇水平男性低于50mg/分升、女性低于55mg/分升（分别为1.3或1.4mmol/升）的患者。患者被随机分配接受缓释烟酸（目标剂量为每日2000mg）或依折麦布（每日10mg）治疗。主要终点是14个月后两组间平均颈总动脉内膜中层厚度相对于基线变化的组间差异。在208例患者完成试验后，根据预先设定的分析，基于疗效提前终止了该试验。
在14个月的研究期间，烟酸组的平均HDL胆固醇水平升高了18.4%，达到50mg/分升（P<0.001），依折麦布组的平均LDL胆固醇水平降低了19.2%，降至66mg/分升（1.7mmol/升）（P<0.001）。烟酸治疗显著降低了LDL胆固醇和甘油三酯水平；依折麦布降低了HDL胆固醇和甘油三酯水平。与依折麦布相比，烟酸在14个月内对平均颈动脉内膜中层厚度变化的疗效更佳（P=0.003），导致平均（P=0.001）和最大颈动脉内膜中层厚度均显著降低（所有比较P≤0.001）。矛盾的是，依折麦布治疗使LDL胆固醇水平更大幅度降低，这与颈动脉内膜中层厚度增加显著相关（R=-0.31，P<0.001）。烟酸组主要心血管事件的发生率低于依折麦布组（1%对5%，卡方检验P=0.04）。
这项比较有效性试验表明，缓释烟酸与他汀类药物联合使用可使颈动脉内膜中层厚度显著消退，且烟酸优于依折麦布。（ClinicalTrials.gov编号，NCT00397657。）
