近日，澳大利亚莫纳什大学Stephen J. Nicholls团队研究了Obicetrapib在高危心血管患者中的安全性和有效性。这一研究成果发表在2025年5月7日出版的《新英格兰医学杂志》上。

Obicetrapib是一种高选择性胆固醇酯转移蛋白抑制剂，可降低低密度脂蛋白（LDL）胆固醇水平。obicetrapib在心血管事件高风险患者中的有效性和安全性尚未得到充分的表征。

研究组进行了一项多国、随机、安慰剂对照试验，纳入了杂合子家族性高胆固醇血症或有动脉粥样硬化性心血管疾病史的患者，这些患者接受了最大耐受剂量的降脂治疗。LDL胆固醇水平为100毫克/分升或更高，非高密度脂蛋白（HDL）胆固醇水平为130毫克/分升或更高，以及LDL胆固醇水平为55至100毫克/分升或非高密度脂蛋白胆固醇水平为85至130毫克/分升且至少有一个额外心血管危险因素的患者符合纳入条件。患者以2:1的比例随机分配，接受10mg obicetrapib每日一次或匹配安慰剂365天。主要终点是LDL胆固醇水平从基线到第84天的百分比变化。

研究组随机分组共2530例患者；1686名患者接受obicetrapib治疗，844名接受安慰剂治疗。患者的平均年龄为65岁，34%为女性，平均基线LDL胆固醇水平为每分升98毫克。obicetrapib组LDL胆固醇水平从基线到第84天的最小二乘平均百分比变化为29.9%（95%可信区间，32.1至27.8），而安慰剂组为2.7%（95% CI， 0.4至5.8） ，组间差异为32.6个百分点（95% CI， 35.8至29.5；P<0.001)。两组的不良事件发生率相似。

研究结果表明，在接受最大耐受剂量降脂治疗且心血管事件高风险的动脉粥样硬化性心血管疾病或杂合性家族性高胆固醇血症患者中，obicetrapib降低了29.9%的LDL胆固醇水平。

附：英文原文

Title: Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk

Author: Stephen J. Nicholls, Adam J. Nelson, Marc Ditmarsch, John J.P. Kastelein, Christie M. Ballantyne, Kausik K. Ray, Ann Marie Navar, Steven E. Nissen, Mariko Harada-Shiba, Danielle L. 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

Issue&Volume: 2025-05-07

Abstract:

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 in the LDL cholesterol level was 29.9% (95% confidence interval [CI], 32.1 to 27.8) in the obicetrapib group, as compared with 2.7% (95% CI, 0.4 to 5.8) in the placebo group, for a between-group difference of 32.6 percentage points (95% CI, 35.8 to 29.5; P<0.001). The incidence of adverse events appeared to be similar in the two groups.

CONCLUSIONS

Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipid-lowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%.

DOI: NJ202505070000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2415820