Title : Cholesteryl ester transfer protein inhibitors in patients with established ASCVD and dyslipidemia: A systematic review and meta-analysis
Abstract:
Introduction: Cholesteryl ester transfer protein inhibitors (CETPis) are known to elevate high-density lipoprotein cholesterol (HDL-C) and reduce low-density lipoprotein cholesterol (LDL-C) levels. However, their clinical efficacy and safety in managing patients with established ASCVD and dyslipidemia are not fully understood. This study provides a comprehensive analysis of the effectiveness and safety of CETPis in patients with established ASCVD and dyslipidemia.
Methods: A comprehensive search of five electronic databases was executed from inception until June 2025 to identify randomized controlled trials (RCTs) comparing CETPi with placebo in patients with ASCVD and dyslipidemia. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE), while secondary endpoints included all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, re-hospitalization, and revascularization. Lipid parameters and safety profile were also investigated. Dichotomous data were pooled as odds ratios (O.R.s) with 95% confidence intervals (C.I.s) using a random-effects model, while the continuous data were analyzed as mean difference (M.D.) with 95% C.I..
Results: 87,272 patients from 16 RCTs were encompassed in this meta-analysis. Anacetrapib revealed a significant reduction in MACE (O.R. = 0.92; 95% CI, 0.86–0.99) and MI (O.R. = 0.86; 95% C.I., 0.81–0.92) compared with placebo. Conversely, torcetrapib was linked to an increased rate of re-hospitalization (O.R. = 1.44; 95% C.I., 1.24–1.68) and all-cause mortality (O.R. = 1.56; 95% C.I., 1.14–2.14). No considerable variations were noticed between CETPi and placebo regarding cardiovascular mortality, stroke, or revascularization. Additionally, CETPi significantly reduced LDL-C, non-HDL-C, triglycerides, and apolipoprotein B (p < 0.001) while increasing HDL-C and apolipoprotein A1 (p < 0.001). Notably, CETPis were linked to an elevated risk of diarrhea.
Conclusion: Anacetrapib lowers MACE and MI risk, while torcetrapib increases mortality and re-hospitalization. CETPi did not significantly affect cardiovascular mortality, stroke, or revascularization versus placebo. CETPi improved lipid profile panel, with overall safety, though CETPis showed higher diarrhea rates.
Keywords: CETPi, CVD, anacetrapib, dalcetrapib, torcetrapib, obicetrapib, evacetrapib.
