Network meta-analysis of 33 RCTs in 120,292 adults: atorvastatin plus obicetrapib ranks best for LDL-C, rosuvastatin plus obicetrapib best for HDL-C (Clin Cardiol 2025)

Original title: Comparative Effectiveness of Cholesteryl Ester Transfer Protein (CETP) Inhibitors on Lipid Profiles in Adults With Hyperlipidemia: A Comprehensive Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials

Clin Cardiol · 1 September 2025 · 7

Khalil I, Islam MR, Promi SA, Joy AD, Sayed MA, Acharjee D, Al-Shammari AS, Abrar S, Jamil TB, Taseen M, Biswas S, Mifty SK et al.

A frequentist network meta-analysis under PRISMA-NMA guidelines pooled 33 randomised controlled trials of CETP inhibitors (anacetrapib, obicetrapib, evacetrapib, dalcetrapib, torcetrapib), alone or with statins, against placebo or other lipid-lowering therapies in 120,292 adults with hyperlipidaemia. Atorvastatin plus obicetrapib gave the largest LDL-C reduction (mean difference -69.00 mg/dL, 95% CI, -95.96 to -42.04), ahead of rosuvastatin plus obicetrapib (-60.70 mg/dL). Rosuvastatin plus obicetrapib gave the greatest HDL-C rise (158.90 mg/dL), ahead of atorvastatin plus obicetrapib (149.90 mg/dL) and obicetrapib monotherapy (139.00 mg/dL), while rosuvastatin plus evacetrapib led on triglyceride reduction. The authors conclude CETP inhibitors, particularly anacetrapib and obicetrapib combined with statins, meaningfully improve lipid profiles. An indirect, class-wide comparison spanning both current and discontinued agents, not a head-to-head trial.

Original abstract

Background: Hyperlipidemia, a key risk factor for cardiovascular disease, is characterized by elevated low-density lipoprotein cholesterol (LDL-C), triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C). Cholesteryl ester transfer protein (CETP) inhibitors, such as anacetrapib, obicetrapib, evacetrapib, dalcetrapib, and torcetrapib, aim to improve lipid profiles by increasing HDL-C and reducing LDL-C, but their comparative efficacy remains unclear.

Methods: This systematic review and frequentist network meta-analysis, conducted per PRISMA-NMA guidelines, included 33 randomized controlled trials (RCTs) involving 120,292 adults with hyperlipidemia. We compared CETP inhibitors, alone or with statins, against placebo or other lipid-lowering therapies. Primary outcome was LDL-C reduction; secondary outcomes included HDL-C, triglycerides, and total cholesterol changes. Random-effects models calculated mean differences (MD) with 95% confidence intervals (CI), and P-scores ranked interventions.

Results: Atorvastatin + obicetrapib showed the largest reduction in LDL-C levels (MD: -69.00, 95% CI: -95.96 to -42.04, p < 0.0001), followed by rosuvastatin + obicetrapib (MD: -60.70, 95% CI: -99.28 to -22.12, p = 0.0020). Atorvastatin + obicetrapib yielded highly significant increase in HDL-C levels (MD: 149.90, 95% CI: 121.70 to 178.10, p < 0.0001), but rosuvastatin + obicetrapib showed the greatest increase (MD: 158.90, 95% CI: 118.59 to 199.21, p < 0.0001) and obicetrapib monotherapy (MD: 139.00, 95% CI: 129.05 to 148.96, p < 0.0001), while rosuvastatin + evacetrapib led triglyceride reductions (MD: -31.70 mg/dL). Rosuvastatin was most effective for total cholesterol (MD: -31.60 mg/dL).

Conclusion: CETP inhibitors, particularly anacetrapib and obicetrapib combined with statins, significantly improve lipid profiles, offering potential therapeutic benefits for hyperlipidemia management and cardiovascular risk reduction.

Trial Registration: The study was registered with PROSPERO to ensure transparency and adherence to methodological rigor (Registration ID: CRD420250652666).

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