Meta-analysis of seven studies: adding a CETP inhibitor to high-intensity statins significantly raises HDL-C and lowers LDL-C with no added adverse events (Front Endocrinol 2025)

Original title: Lipid-lowering effect of combined therapy with high-intensity statins and CETP inhibitors: a Systematic Review and meta-analysis

Front Endocrinol (Lausanne) · 1 January 2025 · 6

Xiang L, Wu H, Zhao Z, Wu T, Lv D, Wu P, Zheng Y, Huang Q, Xu T

A systematic review and meta-analysis of seven studies, drawn from 2,552 initial records, evaluated combining high-intensity statins with CETP inhibitors against statin monotherapy. The combination significantly raised HDL-C (standardised mean difference 2.47, CI 1.77 to 3.18, P < 0.001) and lowered LDL-C (standardised mean difference -1.75, CI -2.19 to -1.31, P < 0.001) compared with statin monotherapy. The authors report the combination also produced a more pronounced rise in apoA-I and reductions in triglycerides and apoB, without increasing adverse events. A class-wide synthesis of statin plus CETP inhibitor combination data rather than a single-drug trial.

Original abstract

Background: This study aimed to evaluate the impact of combining high-intensity statins with CETP inhibitors on lipid levels, as well as to explore their potential clinical significance.

Methods: We conducted a comprehensive search of relevant studies in the PubMed, Embase, Cochrane Library, and Web of Science databases. The Cochrane Risk of Bias Tool RoB 2.0 was employed to evaluate the quality of the included studies. Statistical analyses were carried out using STATA 15 software, with primary outcomes being high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).

Results: Out of 2,552 records, 7 studies were included in the final analysis. The findings revealed that the combination of high-intensity statins with CETP inhibitors significantly raised HDL-C levels (SMD 2.47 [1.77, 3.18], p < 0.001) and lowered LDL-C levels (SMD -1.75 [-2.19, -1.31], p < 0.001).

Conclusion: Compared to statin monotherapy, the combination of high-intensity statins and CETP inhibitors resulted in a more pronounced increase in HDL-C and ApoAI, while reducing LDL-C, triglycerides (TG), and ApoB levels, without increasing the incidence of adverse events.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.