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Dyslipidaemia

LDL-cholesterol lowering with obicetrapib

Nature Reviews Cardiology volume 22, page 463 (2025)Cite this article

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In two clinical trials presented at the European Atherosclerosis Society Congress 2025, treatment with the cholesteryl ester transfer protein (CETP) inhibitor obicetrapib in addition to background lipid-lowering therapy significantly reduced plasma LDL-cholesterol (LDL-C) levels. A large, phase III clinical trial is ongoing to test the effects of obicetrapib on cardiovascular outcomes.

In the phase III TANDEM trial, Ashish Sarraju and colleagues recruited 407 individuals with (or at high risk of) atherosclerotic cardiovascular disease or with heterozygous familial hypercholesterolaemia and who had a plasma LDL-C concentration of ≥1.8 mmol/l (70 mg/dl) despite maximally tolerated lipid-lowering therapy (excluding ezetimibe). Participants were randomly assigned to receive a fixed-dose combination pill containing 10 mg of obicetrapib and 10 mg of ezetimibe, obicetrapib 10-mg monotherapy, ezetimibe 10-mg monotherapy or placebo for 84 days. Obicetrapib–ezetimibe therapy reduced the plasma LDL-C level by 48.6% compared with placebo, by 27.9% compared with ezetimibe monotherapy and by 16.8% compared with obicetrapib monotherapy. Reductions were also observed in plasma non-HDL-C and apolipoprotein B levels compared with baseline, and a greater reduction occurred with the obicetrapib–ezetimibe combination therapy than with either obicetrapib or ezetimibe monotherapy. No significant difference was observed in the rate of adverse events between the groups.

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  • Brandts, J. & Ray, K. K. Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. Nat. Rev. Cardiol. 20, 600–616 (2023)

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Gregory B. Lim

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  1. Gregory B. Lim
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Correspondence to Gregory B. Lim.

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Lim, G.B. LDL-cholesterol lowering with obicetrapib. Nat Rev Cardiol 22, 463 (2025). https://doi.org/10.1038/s41569-025-01173-8

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  • DOI: https://doi.org/10.1038/s41569-025-01173-8

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