A meta-analysis of 62,565 patients confirms CETP inhibitors raise HDL cholesterol by 130 percent yet still fail to reduce cardiovascular events (J Cardiovasc Pharmacol 2026)

Atherosclerotic cardiovascular disease (ASCVD) 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 (RCTs) comparing CETP inhibitors to placebo in patients with ASCVD. 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 to 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 to 1.05), non-fatal myocardial infarction (RR 0.94; 95% CI: 0.87 to 1.02) and stroke (RR 1.02; 95% CI 0.93 to 1.12). Also, no excess risk of adverse events was observed (RR 1.00; 95% CI: 0.99 to 1.02). Conversely, HDL-C (MD + 130.82%; 95% CI: 121.49 to 140.15), LDL-C (MD -32.68%; 95% CI: -40.73 to -24.63), ApoA1 (MD +45.04%; 95% CI: 40.51 to 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.