Obicetrapib Improves Lipid Profile and Reduces Cardiovascular Events, Suggests Study
Australia: A pooled analysis of the phase 3 BROOKLYN and BROADWAY trials showed that obicetrapib, when added to high-intensity statin therapy, significantly lowered LDL-C, ApoB, and Lp(a) levels while increasing HDL-C. The treatment was also associated with a reduced incidence of cardiovascular events compared with placebo.
The study, published in the Journal of the American College of Cardiology (JACC) by Stephen J. Nicholls and colleagues from the Victorian Heart Institute, Monash University, Clayton, Victoria, Australia, explored the effect of the cholesteryl ester transfer protein (CETP) inhibitor obicetrapib on cardiovascular outcomes in high-risk patients. Obicetrapib is known to reduce atherogenic lipids and raise protective HDL-C levels, but its direct impact on cardiovascular event rates had not been fully established until now.
The researchers conducted a pooled analysis involving 2,884 patients—354 with heterozygous familial hypercholesterolemia (HeFH) and 2,530 with established atherosclerotic cardiovascular disease (ASCVD). Participants received either 10 mg of obicetrapib or a placebo daily for 12 months alongside high-intensity statin therapy. The study examined both lipid profile changes and the occurrence of major adverse cardiovascular events (MACE), including coronary heart disease death, myocardial infarction, ischemic stroke, and coronary revascularization.
The analysis led to the following findings:
- The average age of participants was 66 years, and 36% of them were female.
- Baseline median lipid levels were LDL-C 92 mg/dL, HDL-C 48 mg/dL, ApoB 88 mg/dL, non-HDL-C 116 mg/dL, and Lp(a) 40.5 nmol/L.
- Treatment with obicetrapib led to a 37.8% reduction in LDL-C levels.
- ApoB levels decreased by 21.7% following obicetrapib therapy.
- Non-HDL-C levels dropped by 32.4% with obicetrapib treatment.
- Lp(a) levels were reduced by 32.5% in the obicetrapib group.
- HDL-C levels increased significantly by 140% compared to only 1.5% in the placebo group.
- The combined rate of coronary heart disease death, myocardial infarction, ischemic stroke, or coronary revascularization was lower in the obicetrapib group (3.9% vs 5.0%).
- A greater risk reduction was observed after six months of treatment (HR: 0.60).
- When coronary heart disease death, myocardial infarction, and revascularization were analyzed together, the risk was further reduced with obicetrapib (HR: 0.68).
- The reduction was most pronounced beyond the first six months (HR: 0.45).
- Improved lipid parameters—particularly LDL-C, ApoB, non-HDL-C, and Lp(a)—were strongly associated with lower rates of cardiovascular events.
The authors acknowledged that while the pooled analysis provided encouraging signals, the study’s exploratory and relatively short-term design limits definitive conclusions about long-term cardiovascular outcomes. Moreover, event adjudication and post hoc analyses could introduce bias, and most participants had normal baseline Lp(a) levels. Future studies focusing on patients with elevated Lp(a) are needed to assess obicetrapib’s full therapeutic potential.
The ongoing PREVAIL trial, enrolling over 9,000 high-risk patients with suboptimal lipid control, is expected to provide more robust evidence on the long-term cardiovascular benefits of obicetrapib over a three-year treatment period.
"The pooled analysis suggests that obicetrapib, when combined with high-intensity statins, not only improves lipid profiles but also appears to reduce coronary event rates, particularly after prolonged use. If confirmed in larger outcome trials, obicetrapib could emerge as a valuable addition to the current lipid-lowering therapy landscape for preventing cardiovascular disease," the authors concluded.
Reference:
Nicholls SJ, Nelson AJ, Ray KK, Ballantyne CM, Ditmarsch M, Kling D, Hsieh A, Szarek M, Kastelein JJ, Davidson MH. Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis. J Am Coll Cardiol. 2025 Oct 7;86(14):1046-1056. doi: 10.1016/j.jacc.2025.07.056. Epub 2025 Sep 1. PMID: 40888776.
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