Efficacy of Combined Obicetrapib and Ezetimibe Versus Obicetrapib Monotherapy in Patients With Existing or At High Risk for ASCVD: A Comprehensive Review and Meta-analysis

To evaluate the efficacy and safety of obicetrapib and ezetimibe combination therapy compared to obicetrapib monotherapy in patients with, or at high risk for, atherosclerotic cardiovascular disease (ASCVD). A systematic review and meta-analysis was conducted according to Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Obicetrapib plus Ezetimibe with Obicetrapib monotherapy were identified through MEDLINE, Embase, CENTRAL, clinical trial registries, and other databases up to August 2025. The primary outcome was low-density lipoprotein cholesterol (LDL-C) reduction. Secondary outcomes included apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL), high-density lipoprotein cholesterol (HDL), and safety profiles. Data were pooled using a random-effects model, and heterogeneity was assessed with I2 statistics. Three RCTs comprising 338 participants (160 on combination therapy and 156 on monotherapy) were included. The combination significantly reduced LDL-C compared with monotherapy (mean difference [MD] -19.67%; 95% confidence interval [CI]: -22.60 to -16.74; p < 0.00001; I2 = 13%). Greater reductions were also observed in apolipoprotein B (MD -12.8%; 95% CI: -15.15 to -10.55) and non-HDL (MD -20.08%; 95% CI: -21.84 to -18.32), along with an increase in HDL (MD 7.10%; 95% CI: 3.13 to 11.07). Safety outcomes showed no significant group differences, with fewer cardiac and muscular adverse events in the combination arm. Obicetrapib plus Ezetimibe provides clinically meaningful lipid-lowering benefits over Obicetrapib alone without added adverse effects, supporting its value as an oral option for ASCVD patients needing further atherogenic lipoprotein reduction.