Nicholls Stephen J, Nelson Adam J, Ditmarsch Marc, Kastelein John J P, Ballantyne Christie M, Ray Kausik K, Navar Ann Marie, Nissen Steven E, Harada-Shiba Mariko, Curcio Danielle L, Neild Annie, Kling Douglas, Hsieh Andrew, Butters Julie, Ference Brian A, Laufs Ulrich, Banach Maciej, Mehran Roxana, Catapano Alberico L, Huo Yong, Szarek Michael, Balinskaite Violeta, Davidson Michael H
Victorian Heart Institute, Monash University, Clayton, VIC, Australia.
NewAmsterdam Pharma, Amsterdam.
N Engl J Med. 2025 Jul 3;393(1):51-61. doi: 10.1056/NEJMoa2415820. Epub 2025 May 7.
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.
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.
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.
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%. (Funded by NewAmsterdam Pharma; BROADWAY ClinicalTrials.gov number, NCT05142722.).
奥贝胆酸是一种高度选择性的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。在心血管事件高危患者中，奥贝胆酸的疗效和安全性尚未完全明确。
我们进行了一项多国、随机、安慰剂对照试验，纳入了患有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病史且正在接受最大耐受剂量降脂治疗的患者。LDL胆固醇水平为每分升100毫克或更高，或非高密度脂蛋白（HDL）胆固醇水平为每分升130毫克或更高的患者，以及LDL胆固醇水平为每分升55至100毫克或非HDL胆固醇水平为每分升85至130毫克且至少有一项其他心血管危险因素的患者符合纳入标准。患者按2:1的比例随机分组，分别接受每日一次10毫克奥贝胆酸或匹配的安慰剂，为期365天。主要终点是从基线到第84天LDL胆固醇水平的变化百分比。
共有2530例患者进行了随机分组；1686例患者被分配接受奥贝胆酸，844例接受安慰剂。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。奥贝胆酸组从基线到第84天LDL胆固醇水平的最小二乘平均变化百分比为-29.9%（95%置信区间[CI]，-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）。两组不良事件的发生率似乎相似。
在接受最大耐受剂量降脂治疗且心血管事件高危的动脉粥样硬化性心血管疾病或杂合子家族性高胆固醇血症患者中，奥贝胆酸可使LDL胆固醇水平降低29.9%。（由新阿姆斯特丹制药公司资助；BROADWAY ClinicalTrials.gov编号，NCT05142722。）
