SAT-259 Comparative Efficacy of Anacetrapib and Obicetrapib: A Network Meta-Analysis of CETP Inhibitors

Abstract Disclosure: A. Jaber: None. J. Zapen: None. Z. Al-Abed: None. J. Abu Zayed: None. H. Ayesh: None. Introduction: Cholesteryl ester transfer protein (CETP) inhibitors represent an innovative therapeutic approach to dyslipidemia management by modulating lipid profiles, including increasing HDL and reducing LDL cholesterol. Anacetrapib and Obicetrapib are the most promising agents within this class, showing potential for improving lipid parameters associated with cardiovascular risk. This network meta-analysis evaluates the comparative efficacy of these agents in reducing LDL cholesterol, increasing HDL cholesterol, lowering triglycerides, and reducing apolipoprotein B (ApoB). Methods: A systematic search was conducted using PubMed, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov, yielding 22 eligible trials, of which 10 met inclusion criteria. Data were synthesized using a random-effects model to estimate mean differences (MD) with 95% confidence intervals (CI) across key lipid parameters. Results: Both Anacetrapib and Obicetrapib demonstrated significant LDL cholesterol reductions compared to placebo (Anacetrapib: MD -30.18 mg/dL, 95% CI [-39.28; -21.08], p < 0.0001; Obicetrapib: MD -32.40 mg/dL, 95% CI [-44.02; -20.78], p < 0.0001). HDL cholesterol increased markedly, with Obicetrapib showing superior efficacy (Obicetrapib: MD +156.77 mg/dL, 95% CI [117.41; 196.13]; Anacetrapib: MD +103.81 mg/dL, 95% CI [78.43; 129.19], p < 0.0001). Triglycerides were significantly reduced by Anacetrapib (MD -9.15 mg/dL, 95% CI [-14.37; -3.94], p < 0.001), though no substantial reduction was noted with Obicetrapib (MD -2.78 mg/dL, 95% CI [-12.04; 6.49], p = 0.56). Both agents significantly lowered ApoB, with comparable reductions (Anacetrapib: MD -20.83 mg/dL, 95% CI [-26.45; -15.21], p < 0.0001; Obicetrapib: MD -20.67 mg/dL, 95% CI [-27.43; -13.92], p < 0.0001). Conclusions: Anacetrapib and Obicetrapib significantly improve lipid profiles, with Obicetrapib excelling in HDL elevation and Anacetrapib demonstrating superior triglyceride reduction. Both agents are effective in reducing LDL and ApoB. These findings highlight their clinical potential in cardiovascular risk management and underscore the need for further evaluation in larger trials to confirm their safety and long-term efficacy. Presentation: Saturday, July 12, 2025