Tanigawa Ryohei, Nakajima Atsushi, Eguchi Yuichiro, Takahashi Hirokazu, Loomba Rohit, Suganami Hideki, Tanahashi Masaya, Saito Ayumi, Iida Yuki, Yamashita Shizuya
Global Clinical Development Department, Kowa Company Ltd.
Liver Center, Saga University Hospital.
J Atheroscler Thromb. 2025 Jul 1;32(7):823-839. doi: 10.5551/jat.65395. Epub 2024 Dec 18.
In the PEMA-FL study in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), pemafibrate was shown to significantly decrease low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the mechanisms of pemafibrate-induced LDL-C reduction in patients with MASLD by conducting an additional sub-analysis of the PEMA-FL study.
The PEMA-FL study randomized 118 patients with MASLD to receive pemafibrate or placebo for 72 weeks. This sub-analysis examined the percentage change in LDL-C and related lipid markers by tertile of baseline LDL-C levels and the correlation between these changes in the pemafibrate group.
Pemafibrate significantly decreased LDL-C levels approximately 25% (p＜0.001 at all timepoints) from baseline in the highest tertile of baseline LDL-C levels (≥ 137.5 mg/dL), with similar trends for non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) levels. Lipoprotein (a) [Lp(a)] levels decreased only in patients with the highest baseline LDL-C levels. Regardless of the baseline LDL-C levels, pemafibrate altered the LDL particle profile (increased LDL particle size and decreased the number); reduced lathosterol, β-sitosterol, and campesterol; and increased angiopoietin-like protein 3 (ANGPTL3). The percentage change in LDL-C positively correlated with that in ApoB, non-HDL-C, Lp(a), lathosterol, β-sitosterol, and campesterol but not HDL-C and ANGPTL3.
Pemafibrate reduced LDL-C, ApoB, and non-HDL-C levels in patients with MASLD, and the effect was greater in those with higher baseline LDL-C levels. Pemafibrate may clinically benefit patients with MASLD by improving LDL-C levels and the LDL particle profile.
在一项针对代谢功能障碍相关脂肪性肝病（MASLD）患者的PEMA-FL研究中，非诺贝特已被证明能显著降低低密度脂蛋白胆固醇（LDL-C）水平。我们旨在通过对PEMA-FL研究进行额外的亚组分析，来探究非诺贝特降低MASLD患者LDL-C水平的机制。
PEMA-FL研究将118例MASLD患者随机分为两组，分别接受非诺贝特或安慰剂治疗，为期72周。该亚组分析根据基线LDL-C水平的三分位数，研究了LDL-C及相关脂质标志物的百分比变化，以及非诺贝特组这些变化之间的相关性。
在基线LDL-C水平最高三分位数（≥137.5mg/dL）的患者中，非诺贝特使LDL-C水平较基线显著降低约25%（所有时间点p＜0.001），非高密度脂蛋白胆固醇（non-HDL-C）和载脂蛋白B（ApoB）水平也有类似趋势。脂蛋白（a）[Lp（a）]水平仅在基线LDL-C水平最高的患者中降低。无论基线LDL-C水平如何，非诺贝特均改变了LDL颗粒谱（增加LDL颗粒大小并减少数量）；降低了羊毛甾醇、β-谷甾醇和菜油甾醇；并增加了血管生成素样蛋白3（ANGPTL3）。LDL-C的百分比变化与ApoB、non-HDL-C、Lp（a）、羊毛甾醇、β-谷甾醇和菜油甾醇的变化呈正相关，但与HDL-C和ANGPTL3无关。
非诺贝特降低了MASLD患者的LDL-C、ApoB和non-HDL-C水平，且对基线LDL-C水平较高的患者效果更佳。非诺贝特可能通过改善LDL-C水平和LDL颗粒谱，使MASLD患者在临床上获益。
