Efficacy and Safety of CETP Inhibitors in Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Atherosclerotic cardiovascular disease remains a leading cause of death globally. Cholesteryl ester transfer protein (CETP) inhibitors have been proposed as a novel strategy for cardiovascular risk reduction, yet evidence remains inconsistent. PubMed, EMBASE, and Scopus were searched for randomized controlled trials comparing CETP inhibitors with placebo in patients with atherosclerotic cardiovascular disease. Random-effects models were used to pool risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analysis was performed using R software version 4.3.3. We included 5 RCTs involving 62, 565 participants, of whom 31, 698 (50.7%) received CETP inhibitors. Compared with placebo, CETP inhibitors showed no significant reduction in death from coronary heart disease (RR: 0.91; 95% CI, 0.82 to 1.01), unplanned coronary revascularization (RR: 0.91; 95% CI, 0.79–1.05), nonfatal myocardial infarction (RR: 0.94; 95% CI, 0.87–1.02), and stroke (RR: 1.02; 95% CI, 0.93–1.12). In addition, no excess risk of adverse events was observed (RR: 1.00; 95% CI, 0.99–1.02). Conversely, HDL-C (MD: +130.82%; 95% CI, 121.49–140.15), LDL-C (MD: −32.68%; 95% CI, −40.73 to −24.63), ApoA1 (MD: +45.04%; 95% CI, 40.51–49.57), and Apo B (MD: −17.26%; 95% CI, −20.51 to −14.00) showed significant improvement. CETP inhibitors produce substantial lipid modifications but do not reduce major adverse cardiovascular events, underscoring the limitations of surrogate lipid markers and the need for outcome-based validation of lipid-modifying therapies. Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.