Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307, USA.
J Am Coll Cardiol. 2010 Jun 15;55(24):2721-6. doi: 10.1016/j.jacc.2010.03.017.
This report describes the final results of the ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis) trial.
The ARBITER 6-HALTS trial was terminated early on the basis of a pre-specified interim analysis showing superiority of niacin over ezetimibe on change in carotid intima-media thickness (CIMT). After termination, an additional 107 subjects completed a close-out assessment.
Patients with coronary heart disease (CHD) or CHD equivalent with low-density lipoprotein cholesterol <100 mg/dl and high-density lipoprotein cholesterol <50 mg/dl for men or 55 mg/dl for women while receiving stable statin treatment were randomly assigned to ezetimibe (10 mg/day) or extended-release niacin (target dose, 2,000 mg/day). The primary end point was change in mean CIMT, analyzed according to a last observation carried forward method. The relationships of study medication adherence, dosage, and cumulative exposure (product of adherence, dose, and time) with change in CIMT were explored.
Results in 315 patients included 208 with 14-month follow-up and 107 after mean treatment of 7 +/- 3 months. Niacin (n = 154) resulted in significant reduction (regression) in mean CIMT (-0.0102 +/- 0.0026 mm; p < 0.001) and maximal CIMT (-0.0124 +/- 0.0036 mm; p = 0.001), whereas ezetimibe (n = 161) did not reduce mean CIMT (-0.0016 +/- 0.0024 mm; p = 0.88) or maximal CIMT (-0.0005 +/- 0.0029 mm; p = 0.88) compared with baseline. There was a significant difference between ezetimibe and niacin treatment groups on mean changes in CIMT, favoring niacin, for both mean CIMT (p = 0.016) and maximal CIMT (p = 0.01). Increased cumulative drug exposure was related to regression of CIMT with niacin, and progression of CIMT with ezetimibe.
Niacin induces regression of CIMT and is superior to ezetimibe for patients taking statins. (Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis; NCT00397657).
本报告描述了 ARBITER 6-HALTS（动脉生物学研究降低胆固醇 6-HDL 和 LDL 治疗策略在动脉粥样硬化中的治疗效果）试验的最终结果。
ARBITER 6-HALTS 试验因中期分析显示烟酸优于依折麦布在颈动脉内膜中层厚度（CIMT）变化方面的优越性而提前终止。试验终止后，另外 107 名患者完成了一项结束评估。
患有冠心病（CHD）或 CHD 等效疾病、低密度脂蛋白胆固醇<100mg/dl、高密度脂蛋白胆固醇<男性 50mg/dl 或女性 55mg/dl 且正在接受稳定他汀类药物治疗的患者，被随机分配接受依折麦布（10mg/天）或缓释烟酸（目标剂量，2000mg/天）。主要终点是平均 CIMT 的变化，根据最后观察到的向前方法进行分析。探讨了研究药物的依从性、剂量和累积暴露（依从性、剂量和时间的乘积）与 CIMT 变化的关系。
315 名患者的结果包括 208 名接受 14 个月随访和 107 名接受平均治疗 7±3 个月的患者。烟酸（n=154）导致平均 CIMT（-0.0102±0.0026mm；p<0.001）和最大 CIMT（-0.0124±0.0036mm；p=0.001）的显著减少，而依折麦布（n=161）未减少平均 CIMT（-0.0016±0.0024mm；p=0.88）或最大 CIMT（-0.0005±0.0029mm；p=0.88）与基线相比。在平均 CIMT 变化方面，依折麦布和烟酸治疗组之间存在显著差异，烟酸治疗组有利于烟酸，无论是平均 CIMT（p=0.016）还是最大 CIMT（p=0.01）。累积药物暴露的增加与烟酸治疗的 CIMT 回归有关，与依折麦布治疗的 CIMT 进展有关。
烟酸可诱导 CIMT 逆转，对服用他汀类药物的患者优于依折麦布。（依折麦布与缓释烟酸对动脉粥样硬化影响的比较研究；NCT00397657）。
