McKenney James M, Jones Peter H, Bays Harold E, Knopp Robert H, Kashyap Moti L, Ruoff Gary E, McGovern Mark E
National Clinical Research, Richmond, VA 23227, United States.
Atherosclerosis. 2007 Jun;192(2):432-7. doi: 10.1016/j.atherosclerosis.2006.11.037. Epub 2007 Jan 19.
International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.
国际指南建议，对于冠心病（CHD）风险处于中度偏高至高风险的患者，应设定更低的目标胆固醇水平，并对低高密度脂蛋白胆固醇（HDL-C）和甘油三酯升高进行治疗。通常需要联合治疗来实现多个血脂治疗目标，并且部分患者需要将低密度脂蛋白胆固醇（LDL-C）降低≥50%才能达到积极的LDL-C目标。在此背景下，我们评估了低至中剂量的他汀类药物联合缓释烟酸（烟酸ER）、他汀类药物联合依折麦布以及单独使用高效能他汀类药物的联合治疗对血脂水平的比较效果。这是一项开放标签、多中心、为期12周的研究，共纳入292例患者（50%为女性），这些患者根据CHD风险因素数量符合药物治疗标准。患者被随机分为四个平行组，从低剂量滴定至中剂量或高剂量：阿托伐他汀/烟酸ER、瑞舒伐他汀/烟酸ER、辛伐他汀/依折麦布或单独使用瑞舒伐他汀。基线平均值为：LDL-C 197 mg/dL（5.1 mmol/L），HDL-C 49 mg/dL（1.3 mmol/L），甘油三酯168 mg/dL（1.9 mmol/L）。在治疗期间预先设定的时间点，各治疗组LDL-C相对于基线的变化无显著差异。所有组的LDL-C均降低了约50%或更多（范围为-49%至-57%），平均水平达到82 - 98 mg/dL（2.1 - 2.5 mmol/L）。非HDL-C的变化（范围为-46%至-55%）与LDL-C的变化情况相似，各治疗组之间无差异。他汀类药物/烟酸ER联合治疗方案在升高HDL-C和大颗粒HDL（HDL2）以及降低甘油三酯和脂蛋白（a）方面比其他方案更为显著。未观察到与药物相关的肌病或肝毒性。在本研究中，低至中剂量的他汀类药物与烟酸ER联合治疗可广泛控制与CHD独立相关的脂质和脂蛋白。
