Pavanello Chiara, Suppressa Patrizia, Castiglione Sofia, Di Costanzo Alessia, Tramontano Daniele, Rizzi Luigi, Steward Kim, Calabresi Laura, Arca Marcello, Roeters van Lennep Jeanine, D'Erasmo Laura
Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, Milano, Italy.
Department of Internal Medicine and Rare Diseases Centre "C. Frugoni", University of Bari A. Moro, Bari, Italy.
Atherosclerosis. 2025 Feb;401:119089. doi: 10.1016/j.atherosclerosis.2024.119089. Epub 2024 Dec 13.
Homozygous familial hypercholesterolemia (HoFH) is a hereditary lipid metabolism disorder characterized by severe elevation of low-density lipoprotein cholesterol (LDL-C) and heightened risk of premature atherosclerotic cardiovascular disease (ASCVD). Lomitapide, an inhibitor of microsomal triglyceride transfer protein, has shown promise in reducing LDL-C levels, albeit with variable response in real-world settings. Sex-based differences in treatment efficacy and safety remain unclear.
This post-hoc analysis of the Pan-European Lomitapide Study investigated sex-specific disparities in the efficacy and safety of lomitapide in HoFH patients (N=38 women and N=37 men). Data were collected from HoFH patients receiving lomitapide across Europe. Clinical characteristics, lipid profile, and adverse events were compared between women and men. Results indicate comparable baseline characteristics and cardiovascular risk factors between sexes. While LDL-C reduction was comparable at each time point between the two groups, women exhibited a trend towards greater reduction compared to men, particularly evident at 6 months (-53.0% vs -32.9% p=0.051). Annual LDL-C reduction did not differ between sexes (-4.83% ± 7.02 vs -4.03% ± 9.74 p=0.526). No differences in the median lomitapide dose or the intensity of concomitant lipid lowering therapies were observed between sexes. Notably, gastrointestinal disturbances were more prevalent in women (78 events in women vs 32 in men, p=0.0002), although most adverse events were manageable. Event-free survival curves for ASCVD did not significantly differ between sexes (p=0.363).
Lomitapide demonstrates comparable efficacy in reducing LDL-C levels in men and women with HoFH, with potential sex-specific variations in tolerability.
纯合子家族性高胆固醇血症（HoFH）是一种遗传性脂质代谢紊乱疾病，其特征为低密度脂蛋白胆固醇（LDL-C）严重升高以及过早发生动脉粥样硬化性心血管疾病（ASCVD）的风险增加。洛美他派是一种微粒体甘油三酯转移蛋白抑制剂，已显示出降低LDL-C水平的前景，尽管在实际应用中的反应存在差异。治疗效果和安全性的性别差异仍不明确。
这项泛欧洲洛美他派研究的事后分析调查了洛美他派在HoFH患者（38名女性和37名男性）中的疗效和安全性的性别差异。数据收集自欧洲各地接受洛美他派治疗的HoFH患者。比较了女性和男性的临床特征、血脂谱和不良事件。结果表明，两性之间的基线特征和心血管危险因素具有可比性。虽然两组在每个时间点的LDL-C降低幅度相当，但女性与男性相比有更大的降低趋势，在6个月时尤为明显（-53.0%对-32.9%，p=0.051）。两性的年度LDL-C降低幅度无差异（-4.83%±7.02对-4.03%±9.74，p=0.526）。两性之间在洛美他派的中位剂量或联合降脂治疗的强度方面未观察到差异。值得注意的是，胃肠道不适在女性中更为普遍（女性78例事件，男性32例，p=0.0002），尽管大多数不良事件是可控的。ASCVD的无事件生存曲线在两性之间无显著差异（p=0.363）。
洛美他派在降低HoFH男性和女性的LDL-C水平方面显示出相当的疗效，在耐受性方面可能存在性别差异。
