First meta-analysis of nine CETP-inhibitor RCTs finds a class-wide reduction in cardiovascular mortality and myocardial infarction (J Cardiovasc Dev Dis 2024)

Original title: Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

J Cardiovasc Dev Dis · 16 May 2024 · 7

Rehman WU, Yarkoni M, Ilyas MA, Athar F, Javaid M, Ehsan M, Khalid MT, Pasha A, Selma AB, Yarkoni A, Patel K, Sabouni MA et al.

A systematic review and meta-analysis of randomised controlled trials of CETP inhibitors (torcetrapib, dalcetrapib, evacetrapib, anacetrapib, obicetrapib) against placebo, run between 2003 and 2023 with at least 6 months of follow-up. Across nine RCTs, CETP inhibitor use significantly reduced cardiovascular disease-related mortality (risk ratio 0.89, 95% CI, 0.81 to 0.98) and myocardial infarction (risk ratio 0.92, 95% CI, 0.86 to 0.98), an effect the authors attribute primarily to anacetrapib, the largest outcomes trial in the pool. No significant difference emerged for the other secondary outcomes assessed. The authors describe this as the first demonstration that the CETP inhibitor class as a whole associates with reduced cardiovascular mortality and myocardial infarction, a synthesis built on the older generation of trials rather than obicetrapib-specific outcomes data.

Original abstract

Background: Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy.

Methods: We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible.

Primary Outcomes: major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality.

Secondary Outcomes: stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI).

Results: Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; p = 0.02; I2 = 0%); the same studies also reduced the risk of MI (RR = 0.92; 95% CI: 0.86-0.98; p = 0.01; I2 = 0%), which was primarily attributed to anacetrapib. The use of a CETPi did not reduce the likelihood any other outcomes.

Conclusions: Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI.

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