Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk

作者：Stephen J. Nicholls, Adam J. Nelson, Marc Ditmarsch, John J.P. Kastelein, Christie M. Ballantyne, Kausik K. Ray, Ann Marie Návar, Steven E. Nissen, Mariko Harada‐Shiba, Danielle Curcio, Annie Neild, Douglas Kling, Andrew Hsieh, Julie Butters, Brian A. Ference, Ulrich Laufs, Maciej Banach, Roxana Mehran, Alberico L. Catapano, Yong Huo, Michael Szarek, Violeta Balinskaite, Michael H. Davidson · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2415820 · 被引用次数：99 · 研究领域：Lipoproteins and Cardiovascular Health、Diabetes, Cardiovascular Risks, and Lipoproteins、Antiplatelet Therapy and Cardiovascular Diseases

BACKGROUND: Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib have not been fully characterized among patients at high risk for cardiovascular events. METHODS: We conducted a multinational, randomized, placebo-controlled trial involving patients with heterozygous familial hypercholesterolemia or a history of atherosclerotic cardiovascular disease who were receiving maximum tolerated doses of lipid-lowering therapy. Patients with an LDL cholesterol level of 100 mg per deciliter or higher or a non-high-density lipoprotein (HDL) cholesterol level of 130 mg per deciliter or higher, as well as those with an LDL cholesterol level of 55 to 100 mg per deciliter or a non-HDL cholesterol level of 85 to 130 mg per deciliter and at least one additional cardiovascular risk factor, were eligible for inclusion. The patients were randomly assigned in a 2:1 ratio to receive either 10 mg of obicetrapib once daily or matching placebo for 365 days. The primary end point was the percent change in the LDL cholesterol level from baseline to day 84. RESULTS: A total of 2530 patients underwent randomization; 1686 patients were assigned to receive obicetrapib and 844 to receive placebo. The mean age of the patients was 65 years, 34% were women, and the mean baseline LDL cholesterol level was 98 mg per deciliter. The least-squares mean percent change from baseline to day 84...