Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα): Pooled Analysis of Phase 2 and 3 Studies in Dyslipidemic Patients with or without Statin Combination
Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα): Pooled Analysis of Phase 2 and 3 Studies in Dyslipidemic Patients with or without Statin Combination
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DOI：
10.3390/ijms20225537
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Ishibashi, Shun
中科院分区：
文献类型：
--
作者：
Yamashita, Shizuya;Arai, Hidenori;Ishibashi, Shun
尽管他汀类药物能很好地控制低密度脂蛋白胆固醇（LDL-C），但高脂血症已成为心血管事件的独立危险因素。我们汇总了在日本进行的6项pemafibrate随机双盲安慰剂对照研究的前12周数据，并研究了其在使用和不使用他汀类药物的情况下的疗效和安全性，特别关注肾功能不全患者。受试者为1253例患者（“使用他汀类药物”组677例，“不使用他汀类药物”组576例）。在第12周（末次观察值结转），与安慰剂相比，所有pemafibrate剂量（0.1、0.2和0.4 mg/天）（伴或不伴他汀类药物）的甘油三酯（TG）均显著降低（所有组与安慰剂相比p < 0.001）。在“使用他汀类药物”组中，安慰剂组较基线的估计百分比变化为-2.0%，pemafibrate组分别为-45.1%、-48.5%和-50.0%。结果显示，与安慰剂组相比，两组的富TG脂蛋白和致动脉粥样硬化脂质参数均显著降低。不良事件的发生率在pemafibrate组和安慰剂组之间相似，在“他汀类药物治疗”组中有和无肾功能不全的患者之间也相似。与安慰剂相比，培马贝特降低了TG，改善了致动脉粥样硬化的血脂异常，而不良事件没有显著增加，即使在患有肾功能不全的“他汀类药物”患者中也是如此。
Hypertriglyceridemia has emerged as an independent risk factor for cardiovascular events, despite low-density lipoprotein-cholesterol (LDL-C) well-controlled with statins. We pooled data from the first 12 weeks of six randomized double-blind placebo-controlled studies of pemafibrate in Japan and investigated its efficacy and safety with and without statins, particularly focusing on patients with renal dysfunction. Subjects were 1253 patients (677 in the "with-statin" group and 576 in the "without-statin" group). At Week 12 (last observation carried forward), triglyceride (TG) was significantly reduced at all pemafibrate doses (0.1, 0.2, and 0.4 mg/day), both with and without statin, compared to placebo (p < 0.001 vs. placebo for all groups). In the "with-statin" group, the estimated percent change from baseline was -2.0% for placebo and -45.1%, -48.5%, and -50.0%, respectively, for the pemafibrate groups. Findings for both groups showed significant decreases in TG-rich lipoproteins and atherogenic lipid parameters compared to placebo. The incidence of adverse events was similar between the pemafibrate and placebo groups and was also similar for patients with and without renal dysfunction in the "with-statin" group. Pemafibrate lowered TG and improved atherogenic dyslipidemia without a significant increase in adverse events in comparison to the placebo, even among "with-statin" patients who had renal dysfunction.