Efficacy and Safety of Oral PCSK9 Inhibitor Enlicitide in Adults With Heterozygous Familial Hypercholesterolemia

作者：Christie M. Ballantyne, Laura Gellis, Jean-Claude Tardif, Puja Banka, Ann Marie Návar, Emil Andreas Asprusten, Russell L. Scott, Erik S.G. Stroes, Samar Froman, Geraldine Mendizabal, Fan Wang, Alberico L. Catapano · 发表于：JAMA · 年份：2025 · DOI：10.1001/jama.2025.20620 · 被引用次数：51 · 研究领域：Lipoproteins and Cardiovascular Health、Cancer, Lipids, and Metabolism、HIV-related health complications and treatments

Importance: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies. Objective: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy. Design, Setting, and Participants: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least a moderate- or high-intensity statin) and either an LDL-C level of 55 mg/dL or greater and a history of major atherosclerotic cardiovascular disease or an LDL-C level of 70 mg/dL or greater without a history of major atherosclerotic cardiovascular disease. The trial was conducted at 59 sites across 17 countries; the first participant was screened on August 8, 2023, and the last follow-up visit occurred on April 7, 2025. Interventions: Participants were randomized (2:1) to 20 mg of enlicitide (n = 202) or placebo (n = 101) once daily for 52 weeks. Main Outcomes and Measures: The primary outcome was the mean percentage change in LDL-C level at week 24. The secondary outcomes included the mean percentage change in LDL-C level at week ...