Lipid-Lowering Efficacy and Adverse Events of CETP Inhibitor Combination Therapy: A Systematic Review and Network Meta-Analysis.

2025-03-15
Journal of cardiovascular pharmacology 87(4)
- Ping Guo
- Xinlin Yu
- Xinxin Wei
- Xinlin Xiong
- Jie Jiang

PubMed: 41442665
DOI: 10.1097/fjc.0000000000001785

Study Design

Type: Meta-Analysis
Sample size: n = 9,248
Population: 9248 participants from 13 RCTs
Methods: Systematic review and network meta-analysis of 13 RCTs retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025

Background

The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aimed to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs).

Method

Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed through STATA 14.0.

Results

This systematic review and network meta-analysis of 13 studies (9248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3%, respectively).

Conclusions

Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management.

Trial registration

PROSPERO CRD420251145396 ( https://www.crd.york.ac.uk/prospero/ ).