Language
English
Publication Date
10-7-2025
Journal
Journal of the American College of Cardiology
DOI
10.1016/j.jacc.2025.07.056
PMID
40888776
Abstract
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.
Keywords
Aged, Female, Humans, Male, Middle Aged, Anticholesteremic Agents, Atherosclerosis, Cardiovascular Diseases, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Cholesterol, LDL, Double-Blind Method, Esters, Hyperlipoproteinemia Type II, Clinical Trials, Phase III as Topic, Randomized Controlled Trials as Topic, Dicarboxylic Acids, Fatty Acids, cardiovascular risk, cholesteryl ester transfer protein, clinical trials, prevention
Published Open-Access
yes
Recommended Citation
Nicholls, Stephen J; Nelson, Adam J; Ray, Kausik K; et al., "Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis" (2025). Faculty, Staff and Students Publications. 6649.
https://digitalcommons.library.tmc.edu/baylor_docs/6649