Journal Article Review Epublish
PubMed: 42866070 DOI: 10.15420/ecr.2025.88
Beyond Traditional Lipid Lowering: Obicetrapib and the Renaissance of Cholesteryl Ester Transfer Protein Inhibition.
Eur Cardiol 21:e54
Authors: Prashant Thandi, Akshyaya Pradhan, Rajeev Agarwala, Raman Puri, Marco Alfonso Perrone
Affiliations
- Department of Cardiology, King George's Medical University Lucknow, Uttar Pradesh, India.
- Cardiology, Jaswant Rai Specialty Hospital Meerut, Uttar Pradesh, India.
- Cardiology, Cardiac Care Centre New Delhi, India.
- Department of Cardiology and CardioLab, University of Rome Tor Vergata Rome, Italy.
Abstract
Obicetrapib, a next-generation cholesteryl ester transfer protein (CETP) inhibitor, is emerging as a potent therapeutic option to address residual cardiovascular risk in patients not achieving optimal outcomes with existing lipid-lowering therapies, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors. Many high-risk individuals fail to meet recommended LDL cholesterol targets, and up to 40% experience recurrent cardiovascular events, highlighting the need for novel interventions. This review consolidates the evidence from Phase I-III trials (including TULIP, ROSE, BROADWAY, BROOKLYN and TANDEM) and meta-analyses. Take together, the results demonstrate that obicetrapib significantly reduces LDL cholesterol by 30-50%, apolipoprotein B by 20-30% and lipoprotein(a) by as much as 40-50%, while elevating HDL cholesterol levels by more than 100%. The average LDL cholesterol reduction was 0.92 mmol/l (35.4 mg/dl), with amplified effects when combined with ezetimibe. Obicetrapib achieves up to 97% inhibition of CETP activity and maintains a favourable safety profile. Additional metabolic benefits include decreased HbA 1c and a lower incidence of new-onset diabetes. These results highlight obicetrapib's robust efficacy across multiple lipid parameters and its contribution to atherogenic lipoprotein reduction, particularly lipoprotein(a), a marker of high residual risk. Overall, obicetrapib represents a meaningful advancement in cardiovascular risk management and is positioned as an important new agent for high-risk patients with persistent residual risk despite current standard-of-care therapies.
MeSH
Ezetimibe, Lipoproteins, Cholesterol Esters, Risk Management, Cholesterol, Cholesterol Ester Transfer Proteins, Therapeutics, Hydroxymethylglutaryl-Coa Reductase Inhibitors, Lipoprotein(A), Esters