Khoury Etienne, Lauzière Alex, Raal Frederick J, Mancini John, Gaudet Daniel
Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21 Clinical and Translational Research Center, 930 Jacques-Cartier Est, Chicoutimi, Québec, Canada G7H 7K9.
Lipid Clinic, Chicoutimi Hospital, Chicoutimi, Québec, Canada.
Eur Heart J Case Rep. 2023 Jan 17;7(1):ytad029. doi: 10.1093/ehjcr/ytad029. eCollection 2023 Jan.
Homozygous familial hypercholesterolaemia (HoFH) is a rare and life-threatening genetic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels, important xanthomatosis and increased risk of premature atherosclerotic cardiovascular disease. Management of HoFH at an early stage is recommended but conventional lipid-lowering therapies (LLTs) dependent on the LDL-receptor for clearance of LDL particles, are usually not sufficient. However, agents acting independently of the LDL-receptor, such as inhibitors of microsomal triglyceride transfer protein (MTP) or angiopoietin-like protein 3 (ANGPTL3), administered in combination, on top of standard-of-care LLT constitute a promising therapy for HoFH.
The present case describes a long-term (>10 years) follow-up of a 52-year-old woman with severe HoFH, who was treated with conventional lipid-lowering medications (i.e. statins and ezetimibe) for several years before experiencing the risks and benefits that were encountered with the use of LDL-receptor-independent agents (MTP and ANGPTL3 inhibitors). This combination therapy demonstrated a good long-term safety and efficacy profile, while continuous monitoring of hepatic enzymes (sometimes requiring dose adjustments) and fat accumulation is recommended when using lomitapide.
Treating this HoFH patient with an LLT involving the combination of MTP and ANGPTL3 LDL-receptor-independent inhibitors (lomitapide and evinacumab, respectively) showed remarkable improvement in LDL-C levels, disappearance of xanthomatosis and regression in atherosclerotic plaques. In addition to safety and efficacy, one should question the affordability and access hurdle that emerging combination of expensive therapies might constitute in the future for the payers. These challenges could eventually limit the clinical use of those innovative treatments despite their clinical benefit.
纯合子家族性高胆固醇血症（HoFH）是一种罕见的、危及生命的遗传性疾病，其特征为低密度脂蛋白胆固醇（LDL-C）水平极度升高、显著的黄色瘤病以及过早发生动脉粥样硬化性心血管疾病的风险增加。建议早期对HoFH进行管理，但依赖低密度脂蛋白受体清除LDL颗粒的传统降脂疗法（LLT）通常并不充分。然而，在标准治疗LLT的基础上联合使用独立于低密度脂蛋白受体起作用的药物，如微粒体甘油三酯转移蛋白（MTP）抑制剂或血管生成素样蛋白3（ANGPTL3）抑制剂，对HoFH构成了一种有前景的治疗方法。
本病例描述了一名52岁重度HoFH女性的长期（>10年）随访情况，该患者在使用独立于低密度脂蛋白受体的药物（MTP和ANGPTL3抑制剂）之前，已使用传统降脂药物（即他汀类药物和依折麦布）治疗数年。这种联合治疗显示出良好的长期安全性和疗效，而使用洛美他派时建议持续监测肝酶（有时需要调整剂量）和脂肪蓄积情况。
用一种包含MTP和ANGPTL3低密度脂蛋白受体独立抑制剂（分别为洛美他派和依维单抗）的LLT治疗该HoFH患者，显示出LDL-C水平显著改善、黄色瘤病消失以及动脉粥样硬化斑块消退。除了安全性和疗效外，人们还应质疑未来昂贵治疗方法的新组合可能给支付方带来的可负担性和获取障碍。尽管这些创新治疗具有临床益处，但这些挑战最终可能会限制其临床应用。
