Stephen J Nicholls, Adam J Nelson, Kausik K Ray, Christie M Ballantyne, Marc Ditmarsch, Douglas Kling, Andrew Hsieh, Michael Szarek, John J Kastelein, Michael H Davidson
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The association between on-treatment lipids and MACE were also investigated.</p><p><strong>Results: </strong>The cohort (mean age 66 years, 36% female, ASCVD 82%, HeFH 27%, diabetes 35%) had median baseline levels of low-density lipoprotein cholesterol (LDL-C) 92 mg/dL, HDL-C 48 mg/dL, apolipoprotein B (ApoB) 88 mg/dL, non-HDL-C 116 mg/dL, and lipoprotein(a) (Lp(a)) 40.5 nmol/L. Obicetrapib produced greater reductions in LDL-C (-34.0 vs -4.0 mg/dL, -37.8% vs -4.6%), ApoB (-19.0 vs -3.0 mg/dL, -21.7% vs -3.6%), non-HDL-C (-36.0 vs -4.0 mg/dL, -32.4% vs -3.7%), and Lp(a) (-9.8 vs 0 nmol/L, -32.5% vs 0%) and increased HDL-C (+68.0 vs +1.0 mg/dL, +140.0% vs +1.5%). The rate of coronary heart disease death, myocardial infarction, ischemic stroke, or coronary revascularization was lower with obicetrapib (3.9% vs 5.0%; HR: 0.77; 95% CI: 0.54-1.11; P = 0.16), with a risk reduction in the second 6 months (HR: 0.60; 95% CI: 0.37-0.99; P = 0.04). The rate of coronary heart disease death, myocardial infarction, or coronary revascularization was lower with obicetrapib (3.2% vs 4.7%; HR: 0.68; 95% CI: 0.46-1.00; P = 0.048), with a risk reduction in the second 6 months (HR: 0.45; 95% CI: 0.26-0.77; P = 0.003). Achieved levels of LDL-C (P = 0.003), ApoB (P = 0.007), non-HDL-C (P = 0.01), Lp(a) (P = 0.003), and HDL-C (P = 0.0001) were associated with event rates.</p><p><strong>Conclusions: </strong>Obicetrapib treatment associated with a reduction in coronary events, evident beyond 6 months of treatment.</p>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":" ","pages":"1046-1056"},"PeriodicalIF":22.3000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis.\",\"authors\":\"Stephen J Nicholls, Adam J Nelson, Kausik K Ray, Christie M Ballantyne, Marc Ditmarsch, Douglas Kling, Andrew Hsieh, Michael Szarek, John J Kastelein, Michael H Davidson\",\"doi\":\"10.1016/j.jacc.2025.07.056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The cholesteryl ester transfer protein inhibitor obicetrapib decreases levels of atherogenic lipids and raises high-density lipoprotein cholesterol (HDL-C).</p><p><strong>Objectives: </strong>In this study, we sought to determine the effect of obicetrapib on cardiovascular events.</p><p><strong>Methods: </strong>The effects of 10 mg obicetrapib and placebo daily on major adverse cardiovascular event (MACE) rates were investigated in a pooled analysis of 354 patients with heterozygous familial hypercholesterolemia (HeFH) and 2,530 patients with atherosclerotic cardiovascular disease (ASCVD) over 365 days. The association between on-treatment lipids and MACE were also investigated.</p><p><strong>Results: </strong>The cohort (mean age 66 years, 36% female, ASCVD 82%, HeFH 27%, diabetes 35%) had median baseline levels of low-density lipoprotein cholesterol (LDL-C) 92 mg/dL, HDL-C 48 mg/dL, apolipoprotein B (ApoB) 88 mg/dL, non-HDL-C 116 mg/dL, and lipoprotein(a) (Lp(a)) 40.5 nmol/L. Obicetrapib produced greater reductions in LDL-C (-34.0 vs -4.0 mg/dL, -37.8% vs -4.6%), ApoB (-19.0 vs -3.0 mg/dL, -21.7% vs -3.6%), non-HDL-C (-36.0 vs -4.0 mg/dL, -32.4% vs -3.7%), and Lp(a) (-9.8 vs 0 nmol/L, -32.5% vs 0%) and increased HDL-C (+68.0 vs +1.0 mg/dL, +140.0% vs +1.5%). The rate of coronary heart disease death, myocardial infarction, ischemic stroke, or coronary revascularization was lower with obicetrapib (3.9% vs 5.0%; HR: 0.77; 95% CI: 0.54-1.11; P = 0.16), with a risk reduction in the second 6 months (HR: 0.60; 95% CI: 0.37-0.99; P = 0.04). 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引用次数: 0
摘要
背景：胆固醇酯转移蛋白抑制剂obicetrapib降低致动脉粥样硬化性脂质水平并升高高密度脂蛋白胆固醇（HDL-C）。目的：在这项研究中，我们试图确定obicetrapib对心血管事件的影响。方法：对354例杂合子家族性高胆固醇血症（HeFH）患者和2530例动脉粥样硬化性心血管疾病（ASCVD）患者进行365天的汇总分析，研究每日10mg obicetrapib和安慰剂对主要不良心血管事件（MACE）发生率的影响。还研究了治疗期间血脂与MACE之间的关系。结果：该队列（平均年龄66岁，女性36%，ASCVD 82%, HeFH 27%，糖尿病35%）的中位基线水平为低密度脂蛋白胆固醇（LDL-C） 92 mg/dL, HDL-C 48 mg/dL，载脂蛋白B (ApoB) 88 mg/dL，非HDL-C 116 mg/dL，脂蛋白(a) (Lp(a)) 40.5 nmol/L。Obicetrapib产生更大的降低LDL-C (-34.0 vs -4.0 mg/dL, -37.8% vs -4.6%), ApoB (-19.0 vs -3.0 mg/dL, -21.7% vs -3.6%)，非HDL-C (-36.0 vs -4.0 mg/dL, -32.4% vs -3.7%), Lp(a) （-9.8 vs - 0 nmol/L, -32.5% vs 0%）和增加HDL-C （+68.0 vs +1.0 mg/dL, +140.0% vs +1.5%）。obicetrapib的冠心病死亡率、心肌梗死、缺血性卒中或冠状动脉血运重建率较低（3.9% vs 5.0%; HR: 0.77; 95% CI: 0.54-1.11; P = 0.16），后6个月的风险降低（HR: 0.60; 95% CI: 0.37-0.99; P = 0.04）。obicetrapib的冠心病死亡率、心肌梗死或冠状动脉血运重建率较低（3.2% vs 4.7%; HR: 0.68; 95% CI: 0.46-1.00; P = 0.048），第二个6个月的风险降低（HR: 0.45; 95% CI: 0.26-0.77; P = 0.003）。达到的LDL-C （P = 0.003）、ApoB （P = 0.007）、非HDL-C （P = 0.01）、Lp(a) （P = 0.003）和HDL-C （P = 0.0001）水平与事件发生率相关。结论：Obicetrapib治疗与冠状动脉事件的减少相关，明显超过6个月的治疗。
Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis.
Background: The cholesteryl ester transfer protein inhibitor obicetrapib decreases levels of atherogenic lipids and raises high-density lipoprotein cholesterol (HDL-C).
Objectives: In this study, we sought to determine the effect of obicetrapib on cardiovascular events.
Methods: The effects of 10 mg obicetrapib and placebo daily on major adverse cardiovascular event (MACE) rates were investigated in a pooled analysis of 354 patients with heterozygous familial hypercholesterolemia (HeFH) and 2,530 patients with atherosclerotic cardiovascular disease (ASCVD) over 365 days. The association between on-treatment lipids and MACE were also investigated.
Results: The cohort (mean age 66 years, 36% female, ASCVD 82%, HeFH 27%, diabetes 35%) had median baseline levels of low-density lipoprotein cholesterol (LDL-C) 92 mg/dL, HDL-C 48 mg/dL, apolipoprotein B (ApoB) 88 mg/dL, non-HDL-C 116 mg/dL, and lipoprotein(a) (Lp(a)) 40.5 nmol/L. Obicetrapib produced greater reductions in LDL-C (-34.0 vs -4.0 mg/dL, -37.8% vs -4.6%), ApoB (-19.0 vs -3.0 mg/dL, -21.7% vs -3.6%), non-HDL-C (-36.0 vs -4.0 mg/dL, -32.4% vs -3.7%), and Lp(a) (-9.8 vs 0 nmol/L, -32.5% vs 0%) and increased HDL-C (+68.0 vs +1.0 mg/dL, +140.0% vs +1.5%). The rate of coronary heart disease death, myocardial infarction, ischemic stroke, or coronary revascularization was lower with obicetrapib (3.9% vs 5.0%; HR: 0.77; 95% CI: 0.54-1.11; P = 0.16), with a risk reduction in the second 6 months (HR: 0.60; 95% CI: 0.37-0.99; P = 0.04). The rate of coronary heart disease death, myocardial infarction, or coronary revascularization was lower with obicetrapib (3.2% vs 4.7%; HR: 0.68; 95% CI: 0.46-1.00; P = 0.048), with a risk reduction in the second 6 months (HR: 0.45; 95% CI: 0.26-0.77; P = 0.003). Achieved levels of LDL-C (P = 0.003), ApoB (P = 0.007), non-HDL-C (P = 0.01), Lp(a) (P = 0.003), and HDL-C (P = 0.0001) were associated with event rates.
Conclusions: Obicetrapib treatment associated with a reduction in coronary events, evident beyond 6 months of treatment.
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