Pooled analysis of 2,884 patients: obicetrapib cuts coronary events by 32% (HR 0.68) beyond 6 months, ahead of the PREVAIL readout (J Am Coll Cardiol 2025)

Original title: Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis

J Am Coll Cardiol · 1 September 2025 · 9

Nicholls SJ, Nelson AJ, Ray KK, Ballantyne CM, Ditmarsch M, Kling D, Hsieh A, Szarek M, Kastelein JJ, Davidson MH

A pooled analysis of the BROOKLYN (354 patients with heterozygous familial hypercholesterolaemia) and BROADWAY (2,530 patients with atherosclerotic cardiovascular disease) trials examined major adverse cardiovascular events (MACE) over 365 days of obicetrapib 10 mg daily versus placebo (mean age 66, 36% female, 35% with diabetes). Obicetrapib produced larger reductions in LDL-C (-37.8% versus -4.6%), apoB, non-HDL-C and Lp(a), and a larger HDL-C rise (140.0% versus 1.5%). Coronary heart disease death, myocardial infarction, ischaemic stroke or revascularisation occurred less with obicetrapib (3.9% versus 5.0%, hazard ratio 0.77, 95% CI 0.54 to 1.11, P = 0.16), with the effect strengthening after 6 months (hazard ratio 0.60, P = 0.04). The narrower composite excluding stroke fell more (3.2% versus 4.7%, hazard ratio 0.68, 95% CI 0.46 to 1.00, P = 0.048), with a hazard ratio of 0.45 in the second 6 months. Achieved lipid levels tracked with event rates. A pooled post hoc analysis of two trials not powered for cardiovascular outcomes, ahead of the dedicated PREVAIL outcomes trial.

Original abstract

Background: The cholesteryl ester transfer protein inhibitor obicetrapib decreases levels of atherogenic lipids and raises high-density lipoprotein cholesterol (HDL-C).

Objectives: In this study, we sought to determine the effect of obicetrapib on cardiovascular events.

Methods: The effects of 10 mg obicetrapib and placebo daily on major adverse cardiovascular event (MACE) rates were investigated in a pooled analysis of 354 patients with heterozygous familial hypercholesterolemia (HeFH) and 2,530 patients with atherosclerotic cardiovascular disease (ASCVD) over 365 days. The association between on-treatment lipids and MACE were also investigated.

Results: The cohort (mean age 66 years, 36% female, ASCVD 82%, HeFH 27%, diabetes 35%) had median baseline levels of low-density lipoprotein cholesterol (LDL-C) 92 mg/dL, HDL-C 48 mg/dL, apolipoprotein B (ApoB) 88 mg/dL, non-HDL-C 116 mg/dL, and lipoprotein(a) (Lp(a)) 40.5 nmol/L. Obicetrapib produced greater reductions in LDL-C (-34.0 vs -4.0 mg/dL, -37.8% vs -4.6%), ApoB (-19.0 vs -3.0 mg/dL, -21.7% vs -3.6%), non-HDL-C (-36.0 vs -4.0 mg/dL, -32.4% vs -3.7%), and Lp(a) (-9.8 vs 0 nmol/L, -32.5% vs 0%) and increased HDL-C (+68.0 vs +1.0 mg/dL, +140.0% vs +1.5%). The rate of coronary heart disease death, myocardial infarction, ischemic stroke, or coronary revascularization was lower with obicetrapib (3.9% vs 5.0%; HR: 0.77; 95% CI: 0.54-1.11; P = 0.16), with a risk reduction in the second 6 months (HR: 0.60; 95% CI: 0.37-0.99; P = 0.04). The rate of coronary heart disease death, myocardial infarction, or coronary revascularization was lower with obicetrapib (3.2% vs 4.7%; HR: 0.68; 95% CI: 0.46-1.00; P = 0.048), with a risk reduction in the second 6 months (HR: 0.45; 95% CI: 0.26-0.77; P = 0.003). Achieved levels of LDL-C (P = 0.003), ApoB (P = 0.007), non-HDL-C (P = 0.01), Lp(a) (P = 0.003), and HDL-C (P = 0.0001) were associated with event rates.

Conclusions: Obicetrapib treatment associated with a reduction in coronary events, evident beyond 6 months of treatment.

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