Lipid-modifying efficacy and safety of obicetrapib in high-risk cardiovascular patients: A systematic review and meta-analysis

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality, particularly among high-risk patients. Despite the availability of multiple lipid lowering therapies, many patients fail to achieve the guideline recommended low-density lipoprotein cholesterol (LDL-C) targets. Obicetrapib, a cholesteryl ester transfer protein (CETP) inhibitor optimizes lipid profile by blocking the exchange of cholesterol esters from high-density lipoprotein cholesterol (HDL-C) to Apolipoprotein B (ApoB) containing lipoproteins. This study evaluates the efficacy and safety of obicetrapib as an adjunctive therapy in high-risk ASCVD patients. METHODS: Online databases were searched. Outcomes included percentage changes in LDL-C, HDL-C, non-HDL-C, total cholesterol, triglyceride, ApoB, lipoprotein (a) [Lp(a)] and risk of any adverse events (AE), AE leading to discontinuation, acute kidney injury (AKI), transaminase or creatine kinase (CK) elevation and hypertension. Risk ratio (RR) for categorical outcomes and mean difference (MD) for continuous outcomes were reported using 95% confidence intervals (CI). RESULTS: Three studies with 3088 patients (mean age 64 ± 11, 37% female) were selected. Obicetrapib significantly reduced LDL-C (-31.75%), non-HDL-C (-29.35%), triglyceride (-5.61%), Lp(a) (-35.67%), ApoB (-19.37%), and increased HDL-C (+125.94%) with no difference in total cholesterol levels. Obicetrapib was not associated with increased risk for any AE, AE leading to discontinuation, AKI, transaminase or CK elevation, and hypertension. CONCLUSION: Obicetrapib substantially improved lipid profiles in high-risk ASCVD patients on maximally tolerated lipid lowering therapy, without increased short-term adverse events. However, further long-term randomized studies are needed to confirm sustained efficacy, long-term safety, and potential impacts on clinical cardiovascular outcomes.