Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey, USA.
Am J Cardiol. 2012 Sep 15;110(6):817-22. doi: 10.1016/j.amjcard.2012.05.009. Epub 2012 Jun 8.
Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (>6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) ≥4 (primary end point) and the percentage of patients with a maximum GFSS of ≥4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of ≥4 (p <0.001) and the percentage of patients with a maximum GFSS of ≥4 (p <0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.
缓释烟酸(ERN)可改善多种脂质参数,但由于烟酸引起的潮红(NIF)而未被广泛使用。拉罗皮兰(LRPT)可减少 NIF;然而,其对慢性潮红(>6 个月)的影响尚未研究。我们检查了在接受 ERN/LRPT 治疗 20 周后,继续接受 ERN/LRPT 治疗的患者是否比停止 LRPT 并继续单独使用 ERN 的患者经历更少的 NIF。共有 1152 名血脂异常患者被随机分为 2:2:1 组,第 1 组接受 ERN/LRPT 1g/20mg/天,从 0 至 4 周,然后 ERN/LRPT 2g/40mg/天,从 5 至 32 周;第 2 组接受 ERN/LRPT 1g/20mg/天,从 0 至 4 周,然后 ERN/LRPT 2g/40mg/天,从 5 至 20 周,然后在 21 至 32 周期间不使用 LRPT 而服用 ERN 2g/天;或第 3 组接受安慰剂治疗。主要终点是每周中度或更严重的全球潮红严重程度评分(GFSS)≥4 的天数(主要终点),以及在停药期(第 21 至 32 周)期间最大 GFSS≥4 的患者比例(次要终点)。与单独使用 ERN 相比,ERN/LRPT 在停药期间产生的 NIF 明显更少,这可以通过每周 GFSS≥4 的天数(p<0.001)和最大 GFSS≥4 的患者比例(p<0.001;ERN/LRPT 19.6%;ERN 48.9%;安慰剂 9.2%)来衡量。与单独使用 ERN 相比,ERN/LRPT 在停药期间产生的药物相关不良反应更少。在 20 周的稳定维持治疗后,连续接受 ERN/LRPT 治疗的血脂异常患者经历的 NIF 少于停用 LRPT 并继续单独使用 ERN 的患者。总之,我们的研究结果支持 ERN/LRPT 在减少 NIF 症状方面的长期疗效。